Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 36
Filter
2.
Biomed Pharmacother ; 143: 112107, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1372895

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused and is still causing significant mortality and economic consequences all over the globe. As of today, there are three U.S Food and Drug administration (FDA) approved vaccines, Pfizer-BioNTech, Moderna and Janssen COVID-19 vaccine. Also, the antiviral drug remdesivir and two combinations of monoclonal antibodies are authorized for Emergency use (EUA) in certain patients. Furthermore, baricitinib was approved in Japan (April 23, 2021). Despite available vaccines and EUA, pharmacological therapy for the prevention and treatment of COVID-19 is still highly required. There are several ongoing clinical trials investigating the efficacy of clinically available drugs in treating COVID-19. In this study, selected novel pharmacological agents for the possible treatment of COVID-19 will be discussed. Point of discussion will cover mechanism of action, supporting evidence for safety and efficacy and reached stage in development. Drugs were classified into three classes according to the phase of viral life cycle they target. Phase I, the early infective phase, relies on supportive care and symptomatic treatment as needed. In phase II, the pulmonary phase, treatment aims at inhibiting viral entry or replication. Drugs used during this phase are famotidine, monoclonal antibodies, nanobodies, ivermectin, remdesivir, camostat mesylate and other antiviral agents. Finally, phase III, the hyper-inflammatory phase, tocilizumab, dexamethasone, selective serotonin reuptake inhibitors (SSRI), and melatonin are used. The aim of this study is to summarize current findings and suggest gaps in knowledge that can influence future COVID-19 treatment study design.


Subject(s)
Antiviral Agents , COVID-19 Vaccines , COVID-19/drug therapy , Antiviral Agents/classification , Antiviral Agents/pharmacology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/classification , COVID-19 Vaccines/pharmacology , Drug Development , Humans , Medication Therapy Management/trends , SARS-CoV-2 , Treatment Outcome
3.
Nephrology (Carlton) ; 27(2): 195-207, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1352490

ABSTRACT

BACKGROUND: There is a scarcity of data comparing the consequences of first and second COVID-19 waves on kidney transplant recipients (KTRs) in India. METHODS: We conducted a single-centre retrospective study of 259 KTRs with COVID-19 to compare first wave (March 15-December 31 2020, n = 157) and second wave (April 1-May 31 2021, n = 102). RESULTS: KTRs during second wave were younger (43 vs. 40 years; p-value .04) and also included paediatric patients (0 vs. 5.9%; p-value .003). Symptoms were milder during the second wave (45 vs. 62.7%; p-value .007); COVID-19 positive patients had less frequent cough (32 vs. 13.8%; p-value .001), fever was less frequent (58 vs. 37%; p-value .001), and we observed fewer co-morbidities (11 vs. 20.6%; p-value .04). The percentages of neutrophils (77 vs. 83%; p-value .001) and serum ferritin (439 vs. 688; p-value .0006) were higher during second wave, while lymphocyte counts were reduced (20 vs. 14%; p-value .0001). Hydroxychloroquine (11 vs. 0%; p-value .0001) and tocilizumab (7 vs. 0%; p-value .004) were more frequently prescribed during first wave, while utilization of dexamethasone (6 vs. 27%; p-value .0001) and remdesivir (47 vs. 65%; p-value .03) increased during the second wave. Mucormycosis (1.3 vs. 10%; p-value .01) and ICU admissions (20 vs. 37.2%; p-value .002) were more frequent during second wave. The 28-day mortality rate (9.6 vs. 10%; p-value 1) was not different. CONCLUSIONS: There has been a different clinical spectrum of COVID-19 amongst KTR with similar mortality between the two waves at a large Indian transplant centre.


Subject(s)
COVID-19 , Kidney Failure, Chronic , Kidney Transplantation , Transplant Recipients/statistics & numerical data , Adult , Age Factors , Antiviral Agents/administration & dosage , Antiviral Agents/classification , COVID-19/blood , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , Comorbidity , Female , Humans , /statistics & numerical data , India/epidemiology , Intensive Care Units/statistics & numerical data , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Kidney Transplantation/statistics & numerical data , Male , Mortality , Postoperative Period , Retrospective Studies , SARS-CoV-2 , Symptom Assessment/methods , Symptom Assessment/statistics & numerical data
4.
Biomed Pharmacother ; 142: 112015, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1340558

ABSTRACT

COVID-19, an infectious disease, has emerged as one of the leading causes of death worldwide, making it one of the severe public health issues in recent decades. nCoV, the novel SARS coronavirus that causes COVID-19, has brought together scientists in the quest for possible therapeutic and preventive measures. The development of new drugs to manage COVID-19 effectively is a challenging and time-consuming process, thus encouraging extensive investigation of drug repurposing and repositioning candidates. Several medications, including remdesivir, hydroxychloroquine, chloroquine, lopinavir, favipiravir, ribavirin, ritonavir, interferons, azithromycin, capivasertib and bevacizumab, are currently under clinical trials for COVID-19. In addition, several medicinal plants with considerable antiviral activities are potential therapeutic candidates for COVID-19. Statistical data show that the pandemic is yet to slow down, and authorities are placing their hopes on vaccines. Within a short period, four types of vaccines, namely, whole virus, viral vector, protein subunit, and nucleic acid (RNA/DNA), which can confer protection against COVID-19 in different ways, were already in a clinical trial. SARS-CoV-2 variants spread is associated with antibody escape from the virus Spike epitopes, which has grave concerns for viral re-infection and even compromises the effectiveness of the vaccines. Despite these efforts, COVID-19 treatment is still solely based on clinical management through supportive care. We aim to highlight the recent trends in COVID-19, relevant statistics, and clinical findings, as well as potential therapeutics, including in-line treatment methods, preventive measures, and vaccines to combat the prevalence of COVID-19.


Subject(s)
Antiviral Agents , COVID-19 Vaccines , COVID-19/drug therapy , SARS-CoV-2/drug effects , Antiviral Agents/classification , Antiviral Agents/pharmacology , COVID-19/classification , COVID-19/complications , COVID-19/prevention & control , COVID-19 Vaccines/classification , COVID-19 Vaccines/pharmacology , Drug Development/methods , Drug Discovery/methods , Drug Repositioning/methods , Humans
5.
Biomed Res Int ; 2021: 6696012, 2021.
Article in English | MEDLINE | ID: covidwho-1255651

ABSTRACT

A global pandemic has emerged following the appearance of the new severe acute respiratory virus whose official name is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), strongly affecting the health sector as well as the world economy. Indeed, following the emergence of this new virus, despite the existence of a few approved and known effective vaccines at the time of writing this original study, a sense of urgency has emerged worldwide to discover new technical tools and new drugs as soon as possible. In this context, many studies and researches are currently underway to develop new tools and therapies against SARS CoV-2 and other viruses, using different approaches. The 3-chymotrypsin (3CL) protease, which is directly involved in the cotranslational and posttranslational modifications of viral polyproteins essential for the existence and replication of the virus in the host, is one of the coronavirus target proteins that has been the subject of these extensive studies. Currently, the majority of these studies are aimed at repurposing already known and clinically approved drugs against this new virus, but this approach is not really successful. Recently, different studies have successfully demonstrated the effectiveness of artificial intelligence-based techniques to understand existing chemical spaces and generate new small molecules that are both effective and efficient. In this framework and for our study, we combined a generative recurrent neural network model with transfer learning methods and active learning-based algorithms to design novel small molecules capable of effectively inhibiting the 3CL protease in human cells. We then analyze these small molecules to find the correct binding site that matches the structure of the 3CL protease of our target virus as well as other analyses performed in this study. Based on these screening results, some molecules have achieved a good binding score close to -18 kcal/mol, which we can consider as good potential candidates for further synthesis and testing against SARS-CoV-2.


Subject(s)
Antiviral Agents/chemistry , Biological Products/chemistry , Coronavirus 3C Proteases/antagonists & inhibitors , Neural Networks, Computer , Protease Inhibitors/chemistry , SARS-CoV-2/chemistry , Small Molecule Libraries/chemistry , Antiviral Agents/classification , Antiviral Agents/pharmacology , Biological Products/classification , Biological Products/pharmacology , COVID-19/drug therapy , Catalytic Domain , Coronavirus 3C Proteases/chemistry , Coronavirus 3C Proteases/genetics , Coronavirus 3C Proteases/metabolism , Drug Design , Gene Expression , Humans , Kinetics , Molecular Docking Simulation , Protease Inhibitors/classification , Protease Inhibitors/pharmacology , Protein Binding , Protein Interaction Domains and Motifs , Protein Structure, Secondary , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , Small Molecule Libraries/classification , Small Molecule Libraries/pharmacology , Substrate Specificity , Thermodynamics
6.
Int J Biol Macromol ; 183: 1753-1773, 2021 Jul 31.
Article in English | MEDLINE | ID: covidwho-1243010

ABSTRACT

The deficiency of chemical-synthesized antiviral drugs when applied in clinical therapy, such as drug resistance, and the lack of effective antiviral drugs to treat some newly emerging virus infections, such as COVID-19, promote the demand of novelty and safety anti-virus drug candidate from natural functional ingredient. Numerous studies have shown that some polysaccharides sourcing from edible and medicinal fungus (EMFs) exert direct or indirect anti-viral capacities. However, the internal connection of fungus type, polysaccharides structural characteristics, action mechanism was still unclear. Herein, our review focus on the two aspects, on the one hand, we discussed the type of anti-viral EMFs and the structural characteristics of polysaccharides to clarify the structure-activity relationship, on the other hand, the directly or indirectly antiviral mechanism of EMFs polysaccharides, including virus function suppression, immune-modulatory activity, anti-inflammatory activity, regulation of population balance of gut microbiota have been concluded to provide a comprehensive theory basis for better clinical utilization of EMFs polysaccharides as anti-viral agents.


Subject(s)
Agaricales/chemistry , Anti-Inflammatory Agents , Antiviral Agents , COVID-19/drug therapy , Fungal Polysaccharides , Immunologic Factors , SARS-CoV-2/immunology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/classification , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/chemistry , Antiviral Agents/classification , Antiviral Agents/therapeutic use , COVID-19/immunology , COVID-19/prevention & control , Fungal Polysaccharides/chemistry , Fungal Polysaccharides/classification , Fungal Polysaccharides/therapeutic use , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/immunology , Humans , Immunologic Factors/chemistry , Immunologic Factors/classification , Immunologic Factors/therapeutic use
7.
Biophys Chem ; 275: 106608, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1219972

ABSTRACT

This paper proposes natural drug candidate compounds for the treatment of coronavirus disease 2019 (COVID-19). We investigated the binding properties between the compounds in the Moringa oleifera plant and the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 using molecular docking and ab initio fragment molecular orbital calculations. Among the 12 compounds, niaziminin was found to bind the strongest to Mpro. We furthermore proposed novel compounds based on niaziminin and investigated their binding properties to Mpro. The results reveal that the introduction of a hydroxyl group into niaziminin enhances its binding affinity to Mpro. These niaziminin derivatives can be promising candidate drugs for the treatment of COVID-19.


Subject(s)
Antiviral Agents/chemistry , Coronavirus 3C Proteases/antagonists & inhibitors , Moringa oleifera/chemistry , Phytochemicals/chemistry , Protease Inhibitors/chemistry , SARS-CoV-2/chemistry , Thiocarbamates/chemistry , Antiviral Agents/classification , Antiviral Agents/isolation & purification , Antiviral Agents/pharmacology , COVID-19/drug therapy , Catalytic Domain , Coronavirus 3C Proteases/chemistry , Coronavirus 3C Proteases/genetics , Coronavirus 3C Proteases/metabolism , Drug Design , Drug Discovery , Gene Expression , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Phytochemicals/classification , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Protease Inhibitors/classification , Protease Inhibitors/isolation & purification , Protease Inhibitors/pharmacology , Protein Binding , Protein Interaction Domains and Motifs , Protein Structure, Secondary , Quantum Theory , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , Structure-Activity Relationship , Thermodynamics , Thiocarbamates/classification , Thiocarbamates/isolation & purification , Thiocarbamates/pharmacology
9.
Curr Top Med Chem ; 21(6): 442-460, 2021.
Article in English | MEDLINE | ID: covidwho-1183719

ABSTRACT

[Coronaviruses (CoVs) are enveloped positive-stranded RNA viruses with spike (S) protein projections that allow the virus to enter and infect host cells. The S protein is a key virulence factor determining viral pathogenesis, host tropism, and disease pathogenesis. There are currently diverse corona viruses that are known to cause disease in humans. The occurrence of Middle East respiratory syndrome coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), as fatal human CoV diseases, has induced significant interest in the medical field. The novel coronavirus disease (COVID-19) is an infectious disease caused by a novel strain of coronavirus (SAR-CoV-2). The SARS-CoV2 outbreak has been evolved in Wuhan, China, in December 2019, and identified as a pandemic in March 2020, resulting in 53.24 M cases and 1.20M deaths worldwide. SARS-CoV-2 main proteinase (MPro), a key protease of CoV-2, mediates viral replication and transcription. SARS-CoV-2 MPro has been emerged as an attractive target for SARS-CoV-2 drug design and development. Diverse scaffolds have been released targeting SARS-CoV-2 MPro. In this review, we culminate the latest published information about SARS-CoV-2 main proteinase (MPro) and reported inhibitors.


Subject(s)
Antiviral Agents/chemistry , Coronavirus 3C Proteases/antagonists & inhibitors , Phytochemicals/chemistry , Protease Inhibitors/chemistry , SARS-CoV-2/chemistry , Amino Acid Sequence , Antiviral Agents/classification , Antiviral Agents/pharmacology , COVID-19/drug therapy , Catalytic Domain , Coronavirus 3C Proteases/chemistry , Coronavirus 3C Proteases/genetics , Coronavirus 3C Proteases/metabolism , Drug Discovery , Gene Expression , High-Throughput Screening Assays , Humans , Molecular Docking Simulation , Phytochemicals/classification , Phytochemicals/pharmacology , Protease Inhibitors/classification , Protease Inhibitors/pharmacology , Protein Binding , Protein Interaction Domains and Motifs , Protein Structure, Secondary , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , Structure-Activity Relationship
11.
Am J Obstet Gynecol MFM ; 2(3): 100159, 2020 08.
Article in English | MEDLINE | ID: covidwho-1064744

ABSTRACT

Objective: Treatment of coronavirus disease 2019 is mostly symptomatic, but a wide range of medications are under investigation against severe acute respiratory syndrome coronavirus 2. Although pregnant women are excluded from clinical trials, they will inevitably receive therapies whenever they seem effective in nonpregnant patients and even under compassionate use. Methods: We conducted a review of the literature on placental transfer and pregnancy safety data of drugs under current investigation for coronavirus disease 2019. Results: Regarding remdesivir, there are no data in pregnant women. Several other candidates already have safety data in pregnant women, because they are repurposed drugs already used for their established indications. Thus, they may be used in pregnancy, although their safety in the context of coronavirus disease 2019 may differ from conventional use. These include HIV protease inhibitors such as lopinavir/ritonavir that have low placental transfer, interferon that does not cross the placental barrier, and hydroxychloroquine or chloroquine that has high placental transfer. There are also pregnancy safety and placental transfer data for colchicine, steroids, oseltamivir, azithromycin, and some monoclonal antibodies. However, some drugs are strictly prohibited in pregnancy because of known teratogenicity (thalidomide) or fetal toxicities (renin-angiotensin system blockers). Other candidates including tocilizumab, other interleukin 6 inhibitors, umifenovir, and favipiravir have insufficient data on pregnancy outcomes. Conclusion: In life-threatening cases of coronavirus disease 2019, the potential risks of therapy to the fetus may be more than offset by the benefit of curing the mother. Although preclinical and placental transfer studies are required for a number of potential anti-severe acute respiratory syndrome coronavirus 2 drugs, several medications can already be used in pregnant women.


Subject(s)
Abnormalities, Drug-Induced/prevention & control , Antiviral Agents , COVID-19/drug therapy , Drugs, Investigational , Maternal-Fetal Exchange , Pregnancy Complications, Infectious/drug therapy , Abnormalities, Drug-Induced/etiology , Antiviral Agents/adverse effects , Antiviral Agents/classification , Antiviral Agents/pharmacokinetics , Compassionate Use Trials , Drugs, Investigational/adverse effects , Drugs, Investigational/classification , Drugs, Investigational/pharmacokinetics , Female , Humans , Pregnancy , SARS-CoV-2
12.
Infect Dis Health ; 26(1): 63-66, 2021 02.
Article in English | MEDLINE | ID: covidwho-1065111

ABSTRACT

BACKGROUND: Non-therapeutic interventions such as practicing good hand hygiene continue to be the mainstay of protection from SARS-CoV-2 and other emerging respiratory viruses. METHODS: We have evaluated a range of commercially available personal care products including soaps, handwash liquids and alcohol-based hand sanitizers for antiviral efficacy against a clinical isolate of SARS-CoV-2 using internationally accepted standardized protocols at user-relevant contact time-points and product dilutions. RESULTS: All the tested products resulted in 3 to 4 log reduction of SARS-CoV-2 titer. CONCLUSION: Our data re-affirms recommendations by global public health authorities that proper hand hygiene can reduce SARS-CoV-2 viral load significantly which should likely limit spread of the contagion.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/prevention & control , Hand Disinfection/methods , SARS-CoV-2/drug effects , Virus Inactivation/drug effects , Alcohols/pharmacology , Antiviral Agents/classification , Hand Sanitizers/pharmacology , Humans , Soaps/pharmacology
13.
Drug Discov Today ; 26(2): 593-603, 2021 02.
Article in English | MEDLINE | ID: covidwho-1065014

ABSTRACT

The US Food and Drug Administration (FDA) Expanded Access (EA) Program, which allows for compassionate uses of unapproved therapeutics and diagnostics outside of clinical trials, has gained significant traction during the Coronavirus 2019 (COVID-19) pandemic. While development of vaccines has been the major focus, uncertainties around new vaccine safety and effectiveness have spawned interest in other pharmacological options. Experimental drugs can also be approved under the FDA Emergency Use Authorization (EUA) program, designed to combat infectious disease and other threats. Here, we review the US experience in 2020 with pharmacological EA and EUA approvals during the pandemic. We also provide a description of, and clinical rationale for, each of the EA- or EUA-approved drugs (e.g. remdesivir, convalescent plasma, propofol 2%, hydroxychloroquine, ruxolitinib, bamlanivimab, baricitinib, casirivimab plus imdevimab) during the pandemic and concluding reflections on the EA program and its potential future uses.


Subject(s)
Antiviral Agents , COVID-19 Vaccines/pharmacology , COVID-19 , Compassionate Use Trials , Antiviral Agents/classification , Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/epidemiology , COVID-19/prevention & control , Compassionate Use Trials/methods , Compassionate Use Trials/trends , Drug Approval , Humans , SARS-CoV-2 , United States
14.
Biomed Pharmacother ; 137: 111352, 2021 May.
Article in English | MEDLINE | ID: covidwho-1062249

ABSTRACT

INTRODUCTION: The world is witnessing the spread of one of the members of Coronaviruses (CoVs) family, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the 21st century. Considering the short time spent after its prevalence, limited information is known about the effect of the virus mechanism on different organs of the body; meanwhile the lack of specific treatment and vaccine for this virus has exposed millions of people to a big challenge. AREAS COVERED: The review article aims to describe the general and particular characteristics of CoVs, their classification, genome structure, host cell infection, cytokine storm, anti-viral treatments, and inhibition of COVID-19-related ER-mitochondrial stress. In addition, it refers to drugs such as Chloroquine/Hydroxychloroquine, Lopinavir/Ritonavir, darunavir, ribavirin, remdesivir, and favipiravir, which have undergone clinical trials for coronavirus disease 2019 (COVID-19) treatment. This analysis was derived from an extensive scientific literature search including Pubmed, ScienceDirect, and Google Scholar performed. EXPERT OPINION: The effectiveness rate and complications of these drugs can reveal new insights into the potential therapeutic goals for the disease. Moreover, lifestyle change can effectively prevent SARS-CoV-2 infection.


Subject(s)
Antiviral Agents , COVID-19 , SARS-CoV-2 , Antiviral Agents/classification , Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/immunology , COVID-19/physiopathology , Clinical Trials as Topic , Humans , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Treatment Outcome
15.
Biomed Pharmacother ; 137: 111313, 2021 May.
Article in English | MEDLINE | ID: covidwho-1062248

ABSTRACT

The SARS-CoV-2 outbreak and pandemic that began near the end of 2019 has posed a challenge to global health. At present, many candidate small-molecule therapeutics have been developed that can inhibit both the infection and replication of SARS-CoV-2 and even potentially relieve cytokine storms and other related complications. Meanwhile, host-targeted drugs that inhibit cellular transmembrane serine protease (TMPRSS2) can prevent SARS-CoV-2 from entering cells, and its combination with chloroquine and dihydroorotate dehydrogenase (DHODH) inhibitors can limit the spread of SARS-CoV-2 and reduce the morbidity and mortality of patients with COVID-19. The present article provides an overview of these small-molecule therapeutics based on insights from medicinal chemistry research and focuses on RNA-dependent RNA polymerase (RdRp) inhibitors, such as the nucleoside analogues remdesivir, favipiravir and ribavirin. This review also covers inhibitors of 3C-like protease (3CLpro), papain-like protease (PLpro) and other potentially innovative active ingredient molecules, describing their potential targets, activities, clinical status and side effects.


Subject(s)
Antiviral Agents , COVID-19 , Molecular Targeted Therapy/methods , SARS-CoV-2 , Antiviral Agents/classification , Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/metabolism , Enzyme Inhibitors/pharmacology , Humans , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , Therapies, Investigational
16.
Biomed Pharmacother ; 137: 111330, 2021 May.
Article in English | MEDLINE | ID: covidwho-1051491

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causal factor of the coronavirus disease 2019 (COVID-19). Drug repurposing, portraying patented drugs as a successful drug development technique, could shorten the period and minimize costs relative to de novo drug exploration. Recently several drugs have been used as anti-SARS-CoV-2 such as Remdesivir, Favipiravir, Hydroxychloroquine, Azithromycin, Lopinavir/Ritonavir, Nafamostat mesylate and so on. Despite such efforts, there is currently no successful broad-spectrum antiviral countermeasures to combat SARS-CoV-2 or possibly potential CoVs pandemic. Therefore it is desperately important to recognize and test widely efficient, reliable anti-CoV therapies now and in the future. Remdesivir and Favipiravir were more promising despite having side effects; it had prominent efficacy and efficiency while still not yet approved as the official anti-viral drug for SARS CoV-2. In this review, we summarizes the current drug and vaccine discovery status against SARS-CoV-2, predicting that these efforts will help create effective drugs and vaccines for SARS-CoV-2.


Subject(s)
Antiviral Agents , COVID-19 Vaccines , COVID-19 , Antiviral Agents/classification , Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/prevention & control , COVID-19 Vaccines/classification , COVID-19 Vaccines/pharmacology , Humans , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Treatment Outcome
17.
Drug Discov Today ; 26(3): 631-636, 2021 03.
Article in English | MEDLINE | ID: covidwho-1002477

ABSTRACT

The Coronavirus 2019 (COVID-19) pandemic represents the greatest worldwide public health crisis of recent times. The lack of proven effective therapies means that COVID-19 rages relatively unchecked. Current anti-COVID-19 pharmacotherapies are drugs originally designed for other diseases, and administered orally or intravascularly. Thus, they can have various adverse effects. A specific anti-Coronavirus drug should not only target the virus per se, but also treat the related respiratory and cardiovascular symptoms. Here, we examine the advantages and disadvantages of current anti-COVID-19 pharmacotherapies, and analyze the reasons why in the era of big data we have not yet established specific coronavirus therapies and related technical bottlenecks. Finally, we present our design of a novel nebulized S-nitrosocaptopril that is under development for targeting both coronaviruses and their related symptoms.


Subject(s)
Antiviral Agents , COVID-19 , Captopril/analogs & derivatives , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Antiviral Agents/classification , Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/epidemiology , COVID-19/physiopathology , COVID-19/virology , Captopril/pharmacology , Cardiovascular System/drug effects , Cardiovascular System/metabolism , Drug Development/methods , Drug Repositioning/methods , Humans , Nebulizers and Vaporizers , Pharmaceutical Preparations , Respiratory System/diagnostic imaging , Respiratory System/metabolism , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Treatment Outcome
18.
Molecules ; 25(21)2020 Oct 22.
Article in English | MEDLINE | ID: covidwho-983187

ABSTRACT

Viral infections and associated diseases are responsible for a substantial number of mortality and public health problems around the world. Each year, infectious diseases kill 3.5 million people worldwide. The current pandemic caused by COVID-19 has become the greatest health hazard to people in their lifetime. There are many antiviral drugs and vaccines available against viruses, but they have many disadvantages, too. There are numerous side effects for conventional drugs, and active mutation also creates drug resistance against various viruses. This has led scientists to search herbs as a source for the discovery of more efficient new antivirals. According to the World Health Organization (WHO), 65% of the world population is in the practice of using plants and herbs as part of treatment modality. Additionally, plants have an advantage in drug discovery based on their long-term use by humans, and a reduced toxicity and abundance of bioactive compounds can be expected as a result. In this review, we have highlighted the important viruses, their drug targets, and their replication cycle. We provide in-depth and insightful information about the most favorable plant extracts and their derived phytochemicals against viral targets. Our major conclusion is that plant extracts and their isolated pure compounds are essential sources for the current viral infections and useful for future challenges.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , HIV Infections/drug therapy , Hepatitis C, Chronic/drug therapy , Herpes Simplex/drug therapy , Influenza, Human/drug therapy , Phytochemicals/therapeutic use , Pneumonia, Viral/drug therapy , Antiviral Agents/chemistry , Antiviral Agents/classification , Antiviral Agents/isolation & purification , Betacoronavirus/drug effects , Betacoronavirus/pathogenicity , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/pathology , Coronavirus Infections/virology , Drug Discovery , HIV/drug effects , HIV/pathogenicity , HIV/physiology , HIV Infections/pathology , HIV Infections/virology , Hepacivirus/drug effects , Hepacivirus/pathogenicity , Hepacivirus/physiology , Hepatitis C, Chronic/pathology , Hepatitis C, Chronic/virology , Herpes Simplex/pathology , Herpes Simplex/virology , Humans , Influenza, Human/pathology , Influenza, Human/virology , Orthomyxoviridae/drug effects , Orthomyxoviridae/pathogenicity , Orthomyxoviridae/physiology , Pandemics , Phytochemicals/chemistry , Phytochemicals/classification , Phytochemicals/isolation & purification , Plants, Medicinal , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , SARS-CoV-2 , Simplexvirus/drug effects , Simplexvirus/pathogenicity , Simplexvirus/physiology , Virus Internalization/drug effects , Virus Replication/drug effects
19.
Curr Top Med Chem ; 21(6): 507-546, 2021.
Article in English | MEDLINE | ID: covidwho-969520

ABSTRACT

Docking is in demand for the rational computer aided structure based drug design. A review of docking methods and programs is presented. Different types of docking programs are described. They include docking of non-covalent small ligands, protein-protein docking, supercomputer docking, quantum docking, the new generation of docking programs and the application of docking for covalent inhibitors discovery. Taking into account the threat of COVID-19, we present here a short review of docking applications to the discovery of inhibitors of SARS-CoV and SARS-CoV-2 target proteins, including our own result of the search for inhibitors of SARS-CoV-2 main protease using docking and quantum chemical post-processing. The conclusion is made that docking is extremely important in the fight against COVID-19 during the process of development of antivirus drugs having a direct action on SARS-CoV-2 target proteins.


Subject(s)
Antiviral Agents/chemistry , Coronavirus 3C Proteases/antagonists & inhibitors , Molecular Docking Simulation/methods , Prescription Drugs/chemistry , Protease Inhibitors/chemistry , SARS-CoV-2/chemistry , Amino Acid Sequence , Antiviral Agents/classification , Antiviral Agents/pharmacology , COVID-19/drug therapy , Catalytic Domain , Coronavirus 3C Proteases/chemistry , Coronavirus 3C Proteases/genetics , Coronavirus 3C Proteases/metabolism , Drug Design , Drug Repositioning/methods , Gene Expression , Humans , Prescription Drugs/classification , Prescription Drugs/pharmacology , Protease Inhibitors/classification , Protease Inhibitors/pharmacology , Protein Binding , Protein Interaction Domains and Motifs , Protein Structure, Secondary , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , Structure-Activity Relationship
20.
Eur J Pharmacol ; 884: 173381, 2020 Oct 05.
Article in English | MEDLINE | ID: covidwho-959750

ABSTRACT

Outbreak of Coronavirus disease 2019 (COVID-19) started in mid of December 2019 and spread very rapidly across the globe within a month of its outbreak. Researchers all across the globe started working to find out its possible treatments. However, most of initiatives taken were based on various hypotheses and till date no successful treatments have been achieved. Some strategies adopted by China where existing antiviral therapy was initially used to treat COVID-19 have not given very successful results. Researchers from Thailand explored the use of combination of anti-influenza drugs such as Oseltamivir, Lopinavir and Ritonavir to treat it. In some cases, combination therapy of antiviral drugs with chloroquine showed better action against COVID-19. Some of the clinical studies showed very good effect of chloroquine and hydroxychloroquine against COVID-19, however, they were not recommended due to serious clinical toxicity. In some cases, use of rho kinase inhibitor, fasudil was found very effective. In some of the countries, antibody-based therapies have proved fairly successful. The use of BCG vaccines came in light; however, they were not found successful due to lack of full-proof mechanistic studies. In Israel as well as in other developed countries, pluristems allogeneic placental expanded cell therapy has been found successful. Some phytochemicals and nutraceuticals have also been explored to treat it. In a recent report, the use of dexamethasone was found very effective in patients suffering from COVID-19. Its effect was most striking among patients on ventilator. The research for vaccines that can prevent the disease is still going on. In light of the dynamic trends, present review focuses on etiopathogenesis, factors associated with spreading of the virus, and possible strategies to treat this deadly infection. In addition, it attempts to compile the recent updates on development of drugs and vaccines for the dreaded disease.


Subject(s)
Betacoronavirus , Clinical Laboratory Techniques/methods , Communicable Disease Control/methods , Coronavirus Infections , Pandemics , Pneumonia, Viral , Antiviral Agents/classification , Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Betacoronavirus/physiology , COVID-19 , COVID-19 Testing , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Humans , Immunization, Passive/methods , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , SARS-CoV-2 , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL