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1.
Front Pharmacol ; 12: 643619, 2021.
Article in English | MEDLINE | ID: covidwho-1231373

ABSTRACT

COVID-19 is a highly infectious respiratory virus, which can proliferate by invading the ACE2 receptor of host cells. Clinical studies have found that the virus can cause dyspnea, pneumonia and other cardiopulmonary system damage. In severe cases, it can lead to respiratory failure and even death. Although there are currently no effective drugs or vaccines for the prevention and treatment of COVID-19, the patient's prognosis recovery can be effectively improved by ameliorating the dysfunction of the respiratory system, cardiovascular systems, and immune function. Intermittent hypoxic preconditioning (IHP) as a new non-drug treatment has been applied in the clinical and rehabilitative practice for treating chronic obstructive pulmonary disease (COPD), diabetes, coronary heart disease, heart failure, hypertension, and other diseases. Many clinical studies have confirmed that IHP can improve the cardiopulmonary function of patients and increase the cardiorespiratory fitness and the tolerance of tissues and organs to ischemia. This article introduces the physiological and biochemical functions of IHP and proposes the potential application plan of IHP for the rehabilitation of patients with COVID-19, so as to provide a better prognosis for patients and speed up the recovery of the disease. The aim of this narrative review is to propose possible causes and pathophysiology of COVID-19 based on the mechanisms of the oxidative stress, inflammation, and immune response, and to provide a new, safe and efficacious strategy for the better rehabilitation from COVID-19.

2.
Front Pharmacol ; 12: 583279, 2021.
Article in English | MEDLINE | ID: covidwho-1172973

ABSTRACT

The coronavirus disease, 2019 (COVID-19), has spread rapidly around the world and become a major public health problem facing the world. Traditional Chinese medicine (TCM) has been fully committed to treat COVID-19 in China. It improved the clinical symptoms of patients and reduced the mortality rate. In light of the fever was identified as one of leading clinical features of COVID-19, this paper will first analyze the material basis of fever, including pyrogenic cytokines and a variety of the mediators of fever. Then the humoral and neural pathways of fever signal transmission will be described. The scattered evidences about fever recorded in recent years are connected in series. On this basis, the understanding of fever is further deepened from the aspects of pathology and physiology. Finally, combining with the chemical composition and pharmacological action of available TCM, we analyzed the mechanisms of TCMs to play the antipyretic effect through multiple ways. So as to further provide the basis for the research of antipyretic compound preparations of TCMs and explore the potential medicines for the prevention and treatment of COVID-19.

3.
J Chem Inf Model ; 61(4): 2062-2073, 2021 04 26.
Article in English | MEDLINE | ID: covidwho-1157886

ABSTRACT

During almost all 2020, coronavirus disease 2019 (COVID-19) pandemic has constituted the major risk for the worldwide health and economy, propelling unprecedented efforts to discover drugs for its prevention and cure. At the end of the year, these efforts have culminated with the approval of vaccines by the American Food and Drug Administration (FDA) and the European Medicines Agency (EMA) giving new hope for the future. On the other hand, clinical data underscore the urgent need for effective drugs to treat COVID-19 patients. In this work, we embarked on a virtual screening campaign against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Mpro chymotrypsin-like cysteine protease employing our in-house database of peptide and non-peptide ligands characterized by different types of warheads acting as Michael acceptors. To this end, we employed the AutoDock4 docking software customized to predict the formation of a covalent adduct with the target protein. In vitro verification of the inhibition properties of the most promising candidates allowed us to identify two new lead inhibitors that will deserve further optimization. From the computational point of view, this work demonstrates the predictive power of AutoDock4 and suggests its application for the in silico screening of large chemical libraries of potential covalent binders against the SARS-CoV-2 Mpro enzyme.


Subject(s)
COVID-19 , Protease Inhibitors , Antiviral Agents/pharmacology , Humans , Molecular Docking Simulation , Pandemics , Protease Inhibitors/pharmacology , SARS-CoV-2
4.
Futur J Pharm Sci ; 7(1): 72, 2021.
Article in English | MEDLINE | ID: covidwho-1156065

ABSTRACT

BACKGROUND: Ethnomedicine, a study of traditional medicine, is significant in drug discovery and development. African traditional medicine has been in existence for several thousands of years, and several drugs have been discovered and developed from it. MAIN TEXT: The deadly coronavirus disease 2019 (COVID-19) caused by a novel coronavirus known as SARS-CoV-2 has widely spread globally with high mortality and morbidity. Its prevention, treatment and management still pose a serious challenge. A drug for the cure of this disease is yet to be developed. The clinical management at present is based on symptomatic treatment as presented by individuals infected and this is by combination of more than two drugs such as antioxidants, anti-inflammatory, anti-pyretic, and anti-microbials. Literature search was performed through electronic searches of PubMed, Google Scholar, and several research reports including WHO technical documents and monographs. CONCLUSION: Drug discovery from herbs is essential and should be exploited for the discovery of drugs for the management of COVID-19. This review is aimed at identifying ethnomedicinal herbs available in Africa that could be used for the discovery and development of a drug for the prevention, treatment, and management of the novel coronavirus disease 2019.

5.
Biomolecules ; 11(3)2021 03 22.
Article in English | MEDLINE | ID: covidwho-1151739

ABSTRACT

Global processes, such as climate change, frequent and distant travelling and population growth, increase the risk of viral infection spread. Unfortunately, the number of effective and accessible medicines for the prevention and treatment of these infections is limited. Therefore, in recent years, efforts have been intensified to develop new antiviral medicines or vaccines. In this review article, the structure and activity of the most promising antiviral cyanobacterial products are presented. The antiviral cyanometabolites are mainly active against the human immunodeficiency virus (HIV) and other enveloped viruses such as herpes simplex virus (HSV), Ebola or the influenza viruses. The majority of the metabolites are classified as lectins, monomeric or dimeric proteins with unique amino acid sequences. They all show activity at the nanomolar range but differ in carbohydrate specificity and recognize a different epitope on high mannose oligosaccharides. The cyanobacterial lectins include cyanovirin-N (CV-N), scytovirin (SVN), microvirin (MVN), Microcystisviridis lectin (MVL), and Oscillatoria agardhii agglutinin (OAA). Cyanobacterial polysaccharides, peptides, and other metabolites also have potential to be used as antiviral drugs. The sulfated polysaccharide, calcium spirulan (CA-SP), inhibited infection by enveloped viruses, stimulated the immune system's response, and showed antitumor activity. Microginins, the linear peptides, inhibit angiotensin-converting enzyme (ACE), therefore, their use in the treatment of COVID-19 patients with injury of the ACE2 expressing organs is considered. In addition, many cyanobacterial extracts were revealed to have antiviral activities, but the active agents have not been identified. This fact provides a good basis for further studies on the therapeutic potential of these microorganisms.


Subject(s)
Antiviral Agents/chemistry , Cyanobacteria/chemistry , HIV/drug effects , Lectins/pharmacology , Polysaccharides/pharmacology , SARS-CoV-2/drug effects , Simplexvirus/drug effects , Anti-HIV Agents/pharmacology , Antineoplastic Agents/pharmacology , Antiviral Agents/pharmacology , Bacterial Proteins/chemistry , Bacterial Proteins/pharmacology , COVID-19/drug therapy , Carbohydrates/chemistry , Carbohydrates/pharmacology , Cyanobacteria/metabolism , HIV Infections/drug therapy , Humans , Lectins/chemistry , Lectins/metabolism , Polysaccharides/chemistry , Polysaccharides/metabolism
6.
Antimicrob Agents Chemother ; 65(4)2021 03 18.
Article in English | MEDLINE | ID: covidwho-1142997

ABSTRACT

Coronavirus (CoV) disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has claimed many lives worldwide and is still spreading since December 2019. The 3C-like protease (3CLpro) and papain-like protease (PLpro) are essential for maturation of viral polyproteins in SARS-CoV-2 life cycle and thus regarded as key drug targets for the disease. In this study, 3CLpro and PLpro assay platforms were established, and their substrate specificities were characterized. The assays were used to screen collections of 1,068 and 2,701 FDA-approved drugs. After excluding the externally used drugs which are too toxic, we totally identified 12 drugs as 3CLpro inhibitors and 36 drugs as PLpro inhibitors active at 10 µM. Among these inhibitors, six drugs were found to suppress SARS-CoV-2 with the half-maximal effective concentration (EC50) below or close to 10 µM. This study enhances our understanding on the proteases and provides FDA-approved drugs for prevention and/or treatment of COVID-19.


Subject(s)
Antiviral Agents/pharmacology , Peptide Hydrolases/metabolism , Protease Inhibitors/pharmacology , SARS-CoV-2/drug effects , Animals , COVID-19 , Cell Line , Chlorocebus aethiops , Humans , Kinetics , SARS-CoV-2/metabolism , Substrate Specificity , Vero Cells
7.
Heliyon ; 7(2): e06284, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1101243

ABSTRACT

The COVID-19 situation had escalated into an unprecedented global crisis in just a few weeks. On the 30th of January 2020, World Health Organization officially declared the COVID-19 epidemic as a public health emergency of international concern. The confirmed cases were reported to exceed 105,856,046 globally, with the death toll of above 2,311,048, according to the dashboard from Johns Hopkins University on the 7th of February, 2021, though the actual figures may be much higher. Conserved regions of the South Asian strains were used to construct a phylogenetic tree to find evolutionary relationships among the novel virus. Off target similarities were searched with other microorganisms that have been previously reported using Basic Local Alignment Search Tool (BLAST). The conserved regions did not match with any previously reported microorganisms or viruses, which confirmed the novelty of SARS-CoV-2. Currently there is no approved drug for the prevention and treatment of COVID-19, but researchers globally are attempting to come up with one or more soon. Therapeutic strategies need to be addressed urgently to combat COVID-19. Successful drug repurposing is a tool that uses old and safe drugs, is time effective and requires lower development costs, and was thus considered for the study. Molecular docking was used for repurposing drugs from our own comprehensive database of approximately 300 highly characterized, existing drugs with known safety profile, to identify compounds that will inhibit the chosen molecular targets - SARS-CoV-2, ACE2, and TMPRSS2. The study has identified and proposed twenty seven candidates for further in vitro and in vivo studies for the treatment of SARS-CoV-2 infection.

8.
Cochrane Database Syst Rev ; 2: CD013587, 2021 02 12.
Article in English | MEDLINE | ID: covidwho-1098870

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in substantial mortality. Some specialists proposed chloroquine (CQ) and hydroxychloroquine (HCQ) for treating or preventing the disease. The efficacy and safety of these drugs have been assessed in randomized controlled trials. OBJECTIVES: To evaluate the effects of chloroquine (CQ) or hydroxychloroquine (HCQ) for 1) treating people with COVID-19 on death and time to clearance of the virus; 2) preventing infection in people at risk of SARS-CoV-2 exposure; 3) preventing infection in people exposed to SARS-CoV-2. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Current Controlled Trials (www.controlled-trials.com), and the COVID-19-specific resources www.covid-nma.com and covid-19.cochrane.org, for studies of any publication status and in any language. We performed all searches up to 15 September 2020. We contacted researchers to identify unpublished and ongoing studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) testing chloroquine or hydroxychloroquine in people with COVID-19, people at risk of COVID-19 exposure, and people exposed to COVID-19. Adverse events (any, serious, and QT-interval prolongation on electrocardiogram) were also extracted. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility of search results, extracted data from the included studies, and assessed risk of bias using the Cochrane 'Risk of bias' tool. We contacted study authors for clarification and additional data for some studies. We used risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CIs). We performed meta-analysis using a random-effects model for outcomes where pooling of effect estimates was appropriate. MAIN RESULTS: 1. Treatment of COVID-19 disease We included 12 trials involving 8569 participants, all of whom were adults. Studies were from China (4); Brazil, Egypt, Iran, Spain, Taiwan, the UK, and North America (each 1 study); and a global study in 30 countries (1 study). Nine were in hospitalized patients, and three from ambulatory care. Disease severity, prevalence of comorbidities, and use of co-interventions varied substantially between trials. We found potential risks of bias across all domains for several trials. Nine trials compared HCQ with standard care (7779 participants), and one compared HCQ with placebo (491 participants); dosing schedules varied. HCQ makes little or no difference to death due to any cause (RR 1.09, 95% CI 0.99 to 1.19; 8208 participants; 9 trials; high-certainty evidence). A sensitivity analysis using modified intention-to-treat results from three trials did not influence the pooled effect estimate.  HCQ may make little or no difference to the proportion of people having negative PCR for SARS-CoV-2 on respiratory samples at day 14 from enrolment (RR 1.00, 95% CI 0.91 to 1.10; 213 participants; 3 trials; low-certainty evidence). HCQ probably results in little to no difference in progression to mechanical ventilation (RR 1.11, 95% CI 0.91 to 1.37; 4521 participants; 3 trials; moderate-certainty evidence). HCQ probably results in an almost three-fold increased risk of adverse events (RR 2.90, 95% CI 1.49 to 5.64; 1394 participants; 6 trials; moderate-certainty evidence), but may make little or no difference to the risk of serious adverse events (RR 0.82, 95% CI 0.37 to 1.79; 1004 participants; 6 trials; low-certainty evidence). We are very uncertain about the effect of HCQ on time to clinical improvement or risk of prolongation of QT-interval on electrocardiogram (very low-certainty evidence). One trial (22 participants) randomized patients to CQ versus lopinavir/ritonavir, a drug with unknown efficacy against SARS-CoV-2, and did not report any difference for clinical recovery or adverse events. One trial compared HCQ combined with azithromycin against standard care (444 participants). This trial did not detect a difference in death, requirement for mechanical ventilation, length of hospital admission, or serious adverse events. A higher risk of adverse events was reported in the HCQ-and-azithromycin arm; this included QT-interval prolongation, when measured. One trial compared HCQ with febuxostat, another drug with unknown efficacy against SARS-CoV-2 (60 participants). There was no difference detected in risk of hospitalization or change in computed tomography (CT) scan appearance of the lungs; no deaths were reported. 2. Preventing COVID-19 disease in people at risk of exposure to SARS-CoV-2 Ongoing trials are yet to report results for this objective. 3. Preventing COVID-19 disease in people who have been exposed to SARS-CoV-2 One trial (821 participants) compared HCQ with placebo as a prophylactic agent in the USA (around 90% of participants) and Canada. Asymptomatic adults (66% healthcare workers; mean age 40 years; 73% without comorbidity) with a history of exposure to people with confirmed COVID-19 were recruited. We are very uncertain about the effect of HCQ on the primary outcomes, for which few events were reported: 20/821 (2.4%) developed confirmed COVID-19 at 14 days from enrolment, and 2/821 (0.2%) were hospitalized due to COVID-19 (very low-certainty evidence). HCQ probably increases the risk of adverse events compared with placebo (RR 2.39, 95% CI 1.83 to 3.11; 700 participants; 1 trial; moderate-certainty evidence). HCQ may result in little or no difference in serious adverse events (no RR: no participants experienced serious adverse events; low-certainty evidence). One cluster-randomized trial (2525 participants) compared HCQ with standard care for the prevention of COVID-19 in people with a history of exposure to SARS-CoV-2 in Spain. Most participants were working or residing in nursing homes; mean age was 49 years. There was no difference in the risk of symptomatic confirmed COVID-19 or production of antibodies to SARS-CoV-2 between the two study arms. AUTHORS' CONCLUSIONS: HCQ for people infected with COVID-19 has little or no effect on the risk of death and probably no effect on progression to mechanical ventilation. Adverse events are tripled compared to placebo, but very few serious adverse events were found. No further trials of hydroxychloroquine or chloroquine for treatment should be carried out. These results make it less likely that the drug is effective in protecting people from infection, although this is not excluded entirely. It is probably sensible to complete trials examining prevention of infection, and ensure these are carried out to a high standard to provide unambiguous results.


Subject(s)
Antimalarials/therapeutic use , COVID-19/drug therapy , COVID-19/prevention & control , Chloroquine/therapeutic use , Hydroxychloroquine/therapeutic use , SARS-CoV-2 , Adult , Aged , Antimalarials/adverse effects , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , Bias , COVID-19/epidemiology , COVID-19/mortality , COVID-19 Nucleic Acid Testing/statistics & numerical data , Cause of Death , Chloroquine/adverse effects , Humans , Hydroxychloroquine/adverse effects , Middle Aged , Pandemics , Prognosis , Randomized Controlled Trials as Topic , Respiration, Artificial/statistics & numerical data , Standard of Care , Treatment Outcome
9.
Curr Drug Targets ; 22(17): 1986-2005, 2021.
Article in English | MEDLINE | ID: covidwho-1085139

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in December 2019 and has rapidly spread globally. As the confirmed number of cases has reached 83 million worldwide, the potential severity and the deadly complications of the disease requires urgent development of effective drugs for prevention and treatment. No proven effective treatment for this virus currently exists. Most of the antiviral discovery efforts are focused on the repurposing of approved or clinical stage drugs. This review highlights the small-molecule repurposed antiviral agents that are currently under investigation in clinical trials for COVID-19. These include viral polymerase and protease inhibitors remdesivir, galidesivir, favipiravir, ribavirin, sofosbuvir, tenofovir/emtricitabine, baloxavir marboxil, EIDD-2801, lopinavir/ritonavir; virus-/host-directed viral entry and fusion inhibitors arbidol chloroquine/hydroxychloroquine, chlorpromazine, camostat mesylate, nafamostat mesylate, bromhexine and agents with diverse/unclear mechanism of actions as oseltamivir, triazavirin, ivermectin, nitazoxanide, niclosamide and BLD-2660. The published preclinical and clinical data to date on these drugs as well as the mechanisms of action are reviewed.


Subject(s)
Antiviral Agents , COVID-19 , SARS-CoV-2/drug effects , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Clinical Trials as Topic , Drug Repositioning , Humans , Pandemics
10.
Chin J Nat Med ; 18(12): 941-951, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1065694

ABSTRACT

As a representative drug for the treatment of severe community-acquired pneumonia and sepsis, Xuebijing (XBJ) injection is also one of the recommended drugs for the prevention and treatment of coronavirus disease 2019 (COVID-19), but its treatment mechanism for COVID-19 is still unclear. Therefore, this study aims to explore the potential mechanism of XBJ injection in the treatment of COVID-19 employing network pharmacology and molecular docking methods. The corresponding target genes of 45 main active ingredients in XBJ injection and COVID-19 were obtained by using multiple database retrieval and literature mining. 102 overlapping targets of them were screened as the core targets for analysis. Then built the PPI network, TCM-compound-target-disease, and disease-target-pathway networks with the help of Cytoscape 3.6.1 software. After that, utilized DAVID to perform gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to predict the action mechanism of overlapping targets. Finally, by applying molecular docking technology, all compounds were docked with COVID-19 3 CL protease(3CLpro), spike protein (S protein), and angiotensin-converting enzyme II (ACE2). The results indicated that quercetin, luteolin, apigenin and other compounds in XBJ injection could affect TNF, MAPK1, IL6 and other overlapping targets. Meanwhile, anhydrosafflor yellow B (AHSYB), salvianolic acid B (SAB), and rutin could combine with COVID-19 crucial proteins, and then played the role of anti-inflammatory, antiviral and immune response to treat COVID-19. This study revealed the multiple active components, multiple targets, and multiple pathways of XBJ injection in the treatment of COVID-19, which provided a new perspective for the study of the mechanism of traditional Chinese medicine (TCM) in the treatment of COVID-19.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Medicine, Chinese Traditional/methods , Molecular Docking Simulation/methods , SARS-CoV-2 , Signal Transduction/drug effects , Angiotensin-Converting Enzyme 2/metabolism , Biological Availability , COVID-19/drug therapy , COVID-19/metabolism , COVID-19/virology , Coronavirus 3C Proteases/metabolism , Drugs, Chinese Herbal/pharmacokinetics , Drugs, Chinese Herbal/therapeutic use , Humans , Protein Interaction Mapping/methods , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/metabolism
11.
Intest Res ; 20(1): 3-10, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1059852

ABSTRACT

During the coronavirus disease 2019 (COVID-19) pandemic, many unpredictable changes have occurred in the medical field. Risk of COVID-19 does not seem to increase in patients with inflammatory bowel disease (IBD) considering based on current reports. Current medications for IBD do not increase this risk; on the contrary, some of these might be used as therapeutics against COVID-19 and are under clinical trial. Unless the patients have confirmed COVID-19 and severe pneumonia or a high oxygen demand, medical treatment should be continued during the pandemic, except for the use of high-dose corticosteroids. Adherence to general recommendations such as social distancing, wearing facial masks, and vaccination, especially for pneumococcal infections and influenza, is also required. Patients with COVID-19 need to be withhold immunomodulators or biologics for at least 2 weeks and treated based on both IBD and COVID-19 severity. Prevention of IBD relapse caused by sudden medication interruption is important because negative outcomes associated with disease flare up, such as corticosteroid use or hospitalization, are much riskier than medications. The outpatient clinic and infusion center for biologics need to be reserved safe spaces, and endoscopy or surgery should be considered in urgent cases only.

12.
Infect Drug Resist ; 13: 4427-4438, 2020.
Article in English | MEDLINE | ID: covidwho-992957

ABSTRACT

BACKGROUND: COVID-19 caused by SARS-CoV-2 virus emerged as an unprecedented challenge to discover effective drugs for its prevention and cure. Hyperinflammation-induced lung damage is one of the poor prognostic indicators causing a higher rate of morbidity and mortality of COVID-19 patients. Favipiravir, an antiviral drug, is being used for COVID-19 treatment, and we currently have limited information regarding its efficacy and safety. Thus, the present study was undertaken to evaluate the adverse drug events (ADEs) reported in the WHO pharmacovigilance database. METHODS: This study analyzed all suspected ADEs related to favipiravir reported from 2015. The reports were analyzed based on age, gender, and seriousness of ADEs at the System Organ Classification (SOC) level and the individual Preferred Term (PT) level. RESULTS: This study is based on 194 ADEs reported from 93 patients. Most frequent ADEs suspected to be caused by the favipiravir included increased hepatic enzymes, nausea and vomiting, tachycardia, and diarrhea. Severe and fatal ADEs occurred more frequently in men and those over the age of 64 years. Blood and lymphatic disorders, cardiac disorders, hepatobiliary disorders, injury poisoning, and procedural complications were more common manifestations of severe ADEs. CONCLUSION: This study revealed that favipiravir appears to be a relatively safe drug. An undiscovered anti-inflammatory activity of favipiravir may explain the improvement in critically ill patients and reduce inflammatory markers. Currently, the data is based on very few patients. A more detailed assessment of the uncommon ADEs needs to be analyzed when more information will be available.

13.
Iran J Pharm Res ; 19(3): 258-281, 2020.
Article in English | MEDLINE | ID: covidwho-994888

ABSTRACT

The emergence of a novel Coronavirus disease (COVID-19) inducing acute respiratory distress syndrome (ARDS) was identified in Hubei province of China in December 2019 and rapidly spread worldwide as pandemic and became a public health concern. COVID-19 disease is caused by a new virus known as SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), which has recently offered many challenges and efforts to identify effective drugs for its prevention and treatment. Currently, there is no proven effective approach and medication against this virus. Quickly expanding clinical trials and studies on Coronavirus disease 2019 increase our knowledge regarding SARS-CoV-2 virus and introduce several potential drugs targeting virus moiety or host cell elements. Overall, 3 stages were suggested for SARS-CoV-2 infection according to the disease severity, clinical manifestations, and treatment outcomes, including mild, moderate, and severe. This review aimed to classify and summarize several medications and potential therapies according to the disease 3 stages; however, it is worth noting that no medication and therapy has been effective so far.

14.
Eur J Pharmacol ; 883: 173348, 2020 Sep 15.
Article in English | MEDLINE | ID: covidwho-959746

ABSTRACT

The global pandemic of coronavirus disease 2019 (COVID-19), caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in over 7,273,958 cases with almost over 413,372 deaths worldwide as per the WHO situational report 143 on COVID-19. There are no known treatment regimens with proven efficacy and vaccines thus far, posing an unprecedented challenge to identify effective drugs and vaccines for prevention and treatment. The urgency for its prevention and cure has resulted in an increased number of proposed treatment options. The high rate and volume of emerging clinical trials on therapies for COVID-19 need to be compared and evaluated to provide scientific evidence for effective medical options. Other emerging non-conventional drug discovery techniques such as bioinformatics and cheminformatics, structure-based drug design, network-based methods for prediction of drug-target interactions, artificial intelligence (AI) and machine learning (ML) and phage technique could provide alternative routes to discovering potent Anti-SARS-CoV2 drugs. While drugs are being repurposed and discovered for COVID-19, novel drug delivery systems will be paramount for efficient delivery and avoidance of possible drug resistance. This review describes the proposed drug targets for therapy, and outcomes of clinical trials that have been reported. It also identifies the adopted treatment modalities that are showing promise, and those that have failed as drug candidates. It further highlights various emerging therapies and future strategies for the treatment of COVID-19 and delivery of Anti-SARS-CoV2 drugs.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus Infections , Drug Development/methods , Drug Discovery/methods , Pandemics , Pneumonia, Viral , Betacoronavirus/drug effects , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Humans , Pandemics/prevention & control , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , SARS-CoV-2
15.
Pulm Pharmacol Ther ; 66: 101978, 2021 02.
Article in English | MEDLINE | ID: covidwho-947382

ABSTRACT

The recent pandemic of COVID-19 caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an extraordinary challenge to identify effective drugs for prevention and treatment. The pathogenesis implicate acute respiratory disorder (ARD) which is attributed to significantly triggered "cytokine storm" and compromised immune system. This article summarizes the likely benefits of roflumilast, a Phosphodiesterase-4 (PDE-4) inhibitor as a comprehensive support COVID-19 pathogenesis. Roflumilast, a well-known anti-inflammatory and immunomodulatory drug, is protective against respiratory models of chemical and smoke induced lung damage. There is significant data which demonstrate the protective effect of PDE-4 inhibitor in respiratory viral models and is likely to be beneficial in combating COVID-19 pathogenesis. Roflumilast is effective in patients with severe COPD by reducing the rate of exacerbations with the improvement of the lung function, which might further be beneficial for better clinical outcomes in COVID-19 patients. However, further clinical trials are warranted to examine this conjecture.


Subject(s)
Aminopyridines/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Benzamides/therapeutic use , COVID-19/drug therapy , Phosphodiesterase 4 Inhibitors/therapeutic use , Aminopyridines/adverse effects , Aminopyridines/pharmacology , Anti-Inflammatory Agents/adverse effects , Anti-Inflammatory Agents/pharmacology , Benzamides/adverse effects , Benzamides/pharmacology , COVID-19/immunology , Cyclopropanes/adverse effects , Cyclopropanes/pharmacology , Cyclopropanes/therapeutic use , Cytokines/biosynthesis , Inflammation Mediators/metabolism , Pandemics , Phosphodiesterase 4 Inhibitors/adverse effects , Phosphodiesterase 4 Inhibitors/pharmacology
16.
BMC Complement Med Ther ; 20(1): 353, 2020 Nov 23.
Article in English | MEDLINE | ID: covidwho-940020

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by severe acute respiratory syndrome coronavirus 2, and responsible for a global pandemic. Despite there being no known vaccines or medicines that prevent or cure COVID-19, many traditional, integrative, complementary and alternative medicines (TICAMs) have been touted as the solution, as well as researched as a potential remedy globally. This study presents a bibliometric analysis of global research trends at the intersection of TICAM and COVID-19. METHODS: SCOPUS, MEDLINE, EMBASE, AMED and PSYCINFO databases were searched on July 5, 2020, with results being exported on the same day. All publication types were included, however, articles were only deemed eligible if they made mention of one or more TICAMs for the potential prevention, treatment, and/or management of COVID-19 or a health issue indirectly resulting from the COVID-19 pandemic. The following eligible article characteristics were extracted: title; author names, affiliations, and countries; DOI; publication language; publication type; publication year; journal (and whether it is TICAM-focused); 2019 impact factor, and TICAMs mentioned. RESULTS: A total of 296 eligible articles were published by 1373 unique authors at 977 affiliations across 56 countries. The most common countries associated with author affiliation included China, the United States, India and Italy. The vast majority of articles were published in English, followed by Chinese. Eligible articles were published across 157 journals, of which 33 were TICAM-focused; a total of 120 journals had a 2019 impact factor, which ranged from 0.17 to 60.392. A total of 327 TICAMs were mentioned across eligible articles, with the most common ones including: traditional Chinese medicine (n = 94), vitamin D (n = 67), melatonin (n = 16), phytochemicals (n = 12), and general herbal medicine (n = 11). CONCLUSIONS: This study provides researchers and clinicians with a greater knowledge of the characteristics of articles that been published globally at the intersection of COVID-19 and TICAM to date. At a time where safe and effective vaccines and medicines for the prevention and treatment of COVID-19 have yet to be discovered, this study provides a current snapshot of the quantity and characteristics of articles written at the intersection of TICAM therapies and COVID-19.


Subject(s)
Biomedical Research , Coronavirus Infections/drug therapy , Integrative Medicine , Medicine, Chinese Traditional , Pandemics , Pneumonia, Viral/drug therapy , Betacoronavirus , Bibliometrics , Biomedical Research/trends , COVID-19 , China/epidemiology , Complementary Therapies , Coronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Databases, Factual , Drugs, Chinese Herbal , Humans , India/epidemiology , Italy/epidemiology , Melatonin/therapeutic use , Phytotherapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Publishing , SARS-CoV-2 , United States/epidemiology , Vitamin D/therapeutic use
17.
Channels (Austin) ; 14(1): 403-412, 2020 12.
Article in English | MEDLINE | ID: covidwho-889445

ABSTRACT

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted an urgent need to identify effective medicines for the prevention and treatment of the disease. A comparative analysis between SARS-CoV-2 and Hepatitis C Virus (HCV) can expand the available knowledge regarding the virology and potential drug targets against these viruses. Interestingly, comparing HCV with SARS-CoV-2 reveals major similarities between them, ranging from the ion channels that are utilized, to the symptoms that are exhibited by patients. Via this comparative analysis, and from what is known about HCV, the most promising treatments for COVID-19 can focus on the reduction of viral load, treatment of pulmonary system damages, and reduction of inflammation. In particular, the drugs that show most potential in this regard include ritonavir, a combination of peg-IFN, and lumacaftor-ivacaftor. This review anaylses SARS-CoV-2 from the perspective of the role of ion homeostasis and channels in viral pathomechanism. We also highlight other novel treatment approaches that can be used for both treatment and prevention of COVID-19. The relevance of this review is to offer high-quality evidence that can be used as the basis for the identification of potential solutions to the COVID-19 pandemic.


Subject(s)
Betacoronavirus/metabolism , Coronavirus Infections/metabolism , Hepacivirus/metabolism , Ion Channels/metabolism , Pneumonia, Viral/metabolism , Animals , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/pathology , Coronavirus Infections/virology , Hepacivirus/pathogenicity , Hepatitis C/metabolism , Hepatitis C/virology , Humans , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , SARS-CoV-2
18.
J Nepal Health Res Counc ; 18(2): 151-158, 2020 Sep 07.
Article in English | MEDLINE | ID: covidwho-792226

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the strain of coronavirus that causes coronavirus disease 2019 (COVID-19), a respiratory illness. COVID-19 has now become a global public health crisis causing alarming numbers of morbidity and mortality. Ever since the COVID-19 pandemic started scientists, researchers, universities, companies, and institutions all around the world have been endeavoring to discover a potential treatment for COVID-19. Numerous studies and clinical trials on vaccines and drugs for the prevention and treatment of COVID-19 are underway across the world. However, the uncertainty around the efficacy and safety of various treatment regimens have become one of the biggest challenges in the battle against the SARS-CoV-2. This paper is a narrative review of articles regarding the various treatments and vaccines being tested for the SARS-CoV-2, available in the PubMed database along with Google Scholar. There are ongoing clinical trials on potential drugs such as remdesivir, favipiravir, lopinavir/ritonavir, chloroquine, and hydroxychloroquine, corticosteroids tocilizumab, azithromycin, anakinra, etc. and other therapeutic modalities like convalescent plasma therapy. Likewise, vaccines against SARS-CoV-2 are being developed and tested, including mRNA, non-replicating viral vector, DNA, protein subunit candidate vaccines, etc. Although some early-stage clinical trials and studies on these drugs and vaccines have shown positive results, definitive and conclusive results are yet to be obtained. Keywords: COVID-19; antiviral drugs; COVID-19 treatment; COVID-19 vaccine; SARS-CoV-2.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Viral Vaccines , Betacoronavirus , COVID-19 , COVID-19 Vaccines , Clinical Trials as Topic , Coronavirus Infections/drug therapy , Coronavirus Infections/prevention & control , Humans , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , SARS-CoV-2
19.
Medicine (Baltimore) ; 99(32): e21616, 2020 Aug 07.
Article in English | MEDLINE | ID: covidwho-707526

ABSTRACT

BACKGROUND: COVID-19 is a global public health emergency. At present, there is no highly effective medicine for the prevention and treatment of 2019-nCoV. Western medicine for COVID-19 is mainly based on symptomatic support therapy. Chinese herbal medicine has been used to prevent infectious diseases for thousands of years in China. Western medicine routine treatment combined with Chinese herbal medicine is an alternative clinical option but lacks evidence-based medical evidence. The systematic review protocol aims to formulate a research plan that can evaluate the efficacy and safety of western medicine routine treatment combined with Chinese herbal medicine for COVID-19. METHODS: We will search the following eight databases: Cochrane Library, PubMed, Embase, Medline, CNKI, Wanfang, VIP, and CBM. The search time is up to the end of July 2020. Two authors will independently complete literature screening, data extraction, and risk of bias assessment. In case of disagreement, the third author will assist in the judgment. The primary outcome will be the clinical cure rate. The secondary outcome will be accounting symptoms, fever time, time of virus nucleic acid turning negative, check the condition by drawing blood, pneumonia absorption rate, patient hospitalization time, severe conversion rate and case fatality rate, adverse reactions, and adverse events. Revman 5.3 will be used for systematic reviews and meta-analysis. The report of the protocol will follow the PRISMA-P statement, and the report of the systematic review and meta-analysis will follow the PRISMA statement. RESULTS: We will provide evidence-based medical evidence of the efficacy and safety of western medicine routine treatment combined with Chinese herbal medicine for COVID-19. The findings will be published in peer-reviewed journals. REGISTRATION DETAILS: CRD42020190106.


Subject(s)
Anti-Infective Agents/administration & dosage , Antiviral Agents/administration & dosage , Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/administration & dosage , Medicine, Chinese Traditional/methods , Pneumonia, Viral/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , Treatment Outcome , COVID-19 , China , Combined Modality Therapy , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Female , Humans , Male , Pandemics , Patient Safety , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/mortality , Survival Analysis , United States
20.
Epidemiol Infect ; 148: e167, 2020 08 06.
Article in English | MEDLINE | ID: covidwho-696122

ABSTRACT

The outbreak of novel coronavirus pneumonia (coronavirus disease 2019 (COVID-19)), declared as a 'global pandemic' by the World Health Organization (WHO), is a public health emergency of international concern (PHEIC). The outbreak in multiple locations shows a trend of accelerating spread around the world. China has taken a series of powerful measures to contain the spread of the novel coronavirus. In response to the COVID-19 pandemic, in addition to actively finding effective treatment drugs and developing vaccines, it is more important to identify the source of infection at the community level as soon as possible to block the transmission path of the virus to prevent the spread of the pandemic. The implementation of grid management in the community and the adoption of precise management and control measures to reduce unnecessary personnel movement can effectively reduce the risk of pandemic spread. This paper mainly describes that the grid management mode can promote the refinement and comprehensiveness of community management. As a management system with potential to improve the governance ability of community affairs, it may be helpful to strengthen the prevention and control of the epidemic in the community.


Subject(s)
Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Residence Characteristics , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Humans , Pneumonia, Viral/epidemiology
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