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1.
Med Clin (Engl Ed) ; 155(11): 488-490, 2020 Dec 11.
Article in English | MEDLINE | ID: covidwho-1804801

ABSTRACT

INTRODUCTION: There is controversy concerning the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type-I receptor blockers (ARB) for treating hypertensive patients with Covid-19. It has been hypothesized that these drugs might increase the risk of severe Covid-19, but some authors suggested that blocking the renin-angiotensin system might actually decrease this risk. METHODS: Retrospective cohort study of all the consecutive hypertensive patients with confirmed SARS-CoV-2 infection in a health area. The outcome variable was hospitalization because of severe Covid-19. RESULTS: 539 subjects were diagnosed of SARS-CoV-2 infection. Of these, 157 (29.1%) had hypertension and were included in the study. Sixty-nine cases (43.9%) were hospitalized because of severe Covid-19. In multivariable analysis older age, diabetes and hypertensive myocadiopathy were related to a higher risk of hospital admission. ARB treatment was associated with a significantly lower risk of hospitalization (HR: 0.29, 95% CI: 0.10 - 0.88). A similar albeit not significant trend was observed for ACEI. CONCLUSION: ARB or ACEI treatment was not associated with a worse clinical outcome in consecutive hypertensive patients infected by SARS-CoV-2.


INTRODUCCIÓN: Existe controversia respecto al uso de los inhibidores de la enzima convertidora de angiotensina (IECA) o los bloqueadores de los receptores tipo I de la angiotensina II (ARA-II) para el tratamiento de la hipertensión arterial en COVID-19. Se ha sugerido que estos fármacos podrían tanto aumentar como reducir el riesgo de COVID-19 grave. PACIENTES Y MÉTODO: Estudio de cohortes retrospectivo de pacientes consecutivos de un área sanitaria, con hipertensión e infección por SARS-CoV-2. Variable de resultados: ingreso hospitalario por COVID-19 grave. RESULTADOS: Fueron diagnosticados 539 sujetos por infección por SARS-CoV-2. De estos, 157 (29,1%) eran hipertensos y se incluyeron en el estudio. Se ingresaron 69 (43,9%) pacientes por COVID-19 grave. En el análisis multivariante, la edad más elevada, la diabetes y la miocardiopatía hipertensiva se relacionaron con el riesgo de ingreso hospitalario. El tratamiento con ARA-II se asoció con un riesgo significativamente más bajo de ingreso (HR: 0,29, IC 95%: 0,10-0,88). Una tendencia similar, aunque no significativa, se encontró para los IECA. CONCLUSIÓN: el tratamiento con ARA-II o IECA no se asoció con una peor evolución clínica en pacientes hipertensos consecutivos infectados por SARS-CoV-2.

2.
Thromb J ; 18: 22, 2020.
Article in English | MEDLINE | ID: covidwho-1793931

ABSTRACT

BACKGROUND: Hospitals in the Middle East Gulf region have experienced an influx of COVID-19 patients to their medical wards and intensive care units. The hypercoagulability of these patients has been widely reported on a global scale. However, many of the experimental treatments used to manage the various complications of COVID-19 have not been widely studied in this context. The effect of the current treatment protocols on patients' diagnostic and prognostic biomarkers may thus impact the validity of the algorithms adopted. CASE PRESENTATION: In this case series, we report four cases of venous thromboembolism and 1 case of arterial thrombotic event, in patients treated with standard or intensified prophylactic doses of unfractionated heparin or low molecular weight heparin at our institution. Tocilizumab has been utilized as an add-on therapy to the standard of care to treat patients with SARS-CoV-2 associated acute respiratory distress syndrome, in order to dampen the hyperinflammatory response. It is imperative to be aware that this drug may be masking the inflammatory markers (e.g. IL6, CRP, fibrinogen, and ferritin), without reducing the risk of thrombotic events in this population, creating instead a façade of an improved prognostic outcome. However, the D-dimer levels remained prognostically reliable in these cases, as they were not affected by the drug and continued to be at the highest level until event occurrence. CONCLUSIONS: In the setting of tocilizumab therapy, traditional prognostic markers of worsening infection and inflammation, and thus potential risk of acute thrombosis, should be weighed carefully as they may not be reliable for prognosis and may create a façade of an improved prognostic outcome insteasd. Additionally, the fact that thrombotic events continued to be observed despite decrease in inflammatory markers and the proactive anticoagulative approach adopted, raises more questions about the coagulative mechanisms at play in COVID-19, and the appropriate management strategy.

3.
PeerJ ; 8: e9357, 2020.
Article in English | MEDLINE | ID: covidwho-1791913

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a pandemic by the World Health Organization, and the identification of effective therapeutic strategy is a need of the hour to combat SARS-CoV-2 infection. In this scenario, the drug repurposing approach is widely used for the rapid identification of potential drugs against SARS-CoV-2, considering viral and host factors. METHODS: We adopted a host transcriptome-based drug repurposing strategy utilizing the publicly available high throughput gene expression data on SARS-CoV-2 and other respiratory infection viruses. Based on the consistency in expression status of host factors in different cell types and previous evidence reported in the literature, pro-viral factors of SARS-CoV-2 identified and subject to drug repurposing analysis based on DrugBank and Connectivity Map (CMap) using the web tool, CLUE. RESULTS: The upregulated pro-viral factors such as TYMP, PTGS2, C1S, CFB, IFI44, XAF1, CXCL2, and CXCL3 were identified in early infection models of SARS-CoV-2. By further analysis of the drug-perturbed expression profiles in the connectivity map, 27 drugs that can reverse the expression of pro-viral factors were identified, and importantly, twelve of them reported to have anti-viral activity. The direct inhibition of the PTGS2 gene product can be considered as another therapeutic strategy for SARS-CoV-2 infection and could suggest six approved PTGS2 inhibitor drugs for the treatment of COVID-19. The computational study could propose candidate repurposable drugs against COVID-19, and further experimental studies are required for validation.

4.
J Virus Erad ; 6(2): 61-69, 2020 Apr 30.
Article in English | MEDLINE | ID: covidwho-1790484

ABSTRACT

INTRODUCTION: 'Repurposing' existing drugs to treat COVID-19 is vital to reducing mortality and controlling the pandemic. Several promising drugs have been identified and are in various stages of clinical trials globally. If efficacy of these drugs is demonstrated, rapid, mass availability at an affordable cost would be essential to ensuring equity and access especially amongst low- and middle-income economies. METHODS: Minimum costs of production were estimated from the costs of active pharmaceutical ingredients using established methodology, which had good predictive accuracy for medicines for hepatitis C and HIV amongst others. Data were extracted from global export shipment records or analysis of the route of chemical synthesis. The estimated costs were compared with list prices from a range of countries where pricing data were available. RESULTS: Minimum estimated costs of production were US $0.93/day for remdesivir, $1.45/day for favipiravir, $0.08/day for hydroxychloroquine, $0.02/day for chloroquine, $0.10/day for azithromycin, $0.28/day for lopinavir/ritonavir, $0.39/day for sofosbuvir/daclatasvir and $1.09/day for pirfenidone. Costs of production ranged between $0.30 and $31 per treatment course (10-28 days). Current prices of these drugs were far higher than the costs of production, particularly in the US. CONCLUSIONS: Should repurposed drugs demonstrate efficacy against COVID-19, they could be manufactured profitably at very low costs, for much less than current list prices. Estimations for the minimum production costs can strengthen price negotiations and help ensure affordable access to vital treatment for COVID-19 at low prices globally.

5.
Exp Clin Transplant ; 20(3): 285-292, 2022 03.
Article in English | MEDLINE | ID: covidwho-1771685

ABSTRACT

OBJECTIVES: With the declaration of the COVID-19 pandemic and the increased COVID-19 risk shown in transplant recipients, the prevalence, clinical course, and outcomes of COVID-19 infections among liver transplant recipients were assessed. MATERIALS AND METHODS: A questionnaire was designed and used to survey medical services for liver transplant recipients seen at our center in terms of COVID-19 infection. RESULTS: Twenty-five patients infected with COVID-19 were identified from 265 liver transplant recipients. Most patients were male and had COVID-19 despite quarantine at home. All patients received modified immunosuppressive drugs during infection with COVID-19 with minor changes in routine immunosuppressive therapy. Among the identified patients, 21 recovered and 4 patients died. One of the dead patients, in addition to having a liver transplant, had brain cancer with metastasis to the lungs. CONCLUSIONS: In liver transplant recipients infected with COVID-19, immunosuppressive drugs seemed to cause only mild to moderate illnesses or even helped them recover from the disease. However, more evidence is needed to prove this hypothesis. It is also recommended that transplant recipients should be warned about personal hygiene and be monitored closely by organ transplant centers.


Subject(s)
COVID-19 , Kidney Transplantation , Liver Transplantation , Humans , Immunosuppressive Agents/adverse effects , Iran/epidemiology , Kidney Transplantation/adverse effects , Liver Transplantation/adverse effects , Male , Pandemics , Registries , SARS-CoV-2 , Transplant Recipients , Treatment Outcome
6.
J Matern Fetal Neonatal Med ; 35(8): 1610-1618, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1747012

ABSTRACT

Corona virus disease 2019 started in December 2019 as an outbreak of unexplained pneumonias in Wuhan, a city in Hubei province of China. This illness emerged as an epidemic in China and later spread to almost all countries over the globe except Antarctica. This is caused by a beta Corona virus, which is genetically similar to SARS virus. The predominant mode of transmission is via droplet spread, when the infected person coughs, sneezes or talks the virus is released in the respiratory secretions. As there are only a few cases of COVID 19 in neonates, there is no convincing evidence to support the possibility of vertical transmission. Clinical presentation in neonates is nonspecific, commonly observed are temperature instability, respiratory distress, poor feeding, lethargy, vomiting and diarrhea. Laboratory examinations may be nonspecific. Definitive test for 2019-nCoV is the detection of viral nucleic acid by real-time fluorescence polymerase chain reaction (RT-PCR). Suspected and confirmed COVID positive mothers should be delivered in separate delivery rooms and operation theaters. Since there is no approved treatment or drug for this disease, prevention of infection and breaking the chain of transmission plays a crucial role.


Subject(s)
COVID-19 , SARS Virus , COVID-19/diagnosis , Disease Outbreaks , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , SARS-CoV-2
7.
Viruses ; 12(5)2020 05 24.
Article in English | MEDLINE | ID: covidwho-1726014

ABSTRACT

Feline infectious peritonitis (FIP) is a viral disease with a high morbidity and mortality by the FIP virus (FIPV, virulent feline coronavirus). Several antiviral drugs for FIP have been identified, but many of these are expensive and not available in veterinary medicine. Hydroxychloroquine (HCQ) is a drug approved by several countries to treat malaria and immune-mediated diseases in humans, and its antiviral effects on other viral infections (e.g., SARS-CoV-2, dengue virus) have been confirmed. We investigated whether HCQ in association with interferon-ω (IFN-ω) is effective for FIPV in vitro. A total of 100 µM of HCQ significantly inhibited the replication of types I and II FIPV. Interestingly, the combination of 100 µM of HCQ and 104 U/mL of recombinant feline IFN-ω (rfIFN-ω, veterinary registered drug) increased its antiviral activity against type I FIPV infection. Our study suggested that HCQ and rfIFN-ω are applicable for treatment of FIP. Further clinical studies are needed to verify the combination of HCQ and rIFN-ω will be effective and safe treatment for cats with FIP.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus, Feline/drug effects , Hydroxychloroquine/pharmacology , Interferon Type I/pharmacology , Analysis of Variance , Animals , Antiviral Agents/therapeutic use , Antiviral Agents/toxicity , Cats , Cell Line/drug effects , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Coronavirus, Feline/pathogenicity , Drug Combinations , Feline Infectious Peritonitis/drug therapy , Feline Infectious Peritonitis/virology , Fluorescent Antibody Technique/veterinary , Hydroxychloroquine/therapeutic use , Hydroxychloroquine/toxicity , Interferon Type I/therapeutic use , Interferon Type I/toxicity , Virulence
8.
Viruses ; 12(5)2020 04 26.
Article in English | MEDLINE | ID: covidwho-1726007

ABSTRACT

In January 2020, Chinese health agencies reported an outbreak of a novel coronavirus-2 (CoV-2) which can lead to severe acute respiratory syndrome (SARS). The virus, which belongs to the coronavirus family (SARS-CoV-2), was named coronavirus disease 2019 (COVID-19) and declared a pandemic by the World Health Organization (WHO). Full-length genome sequences of SARS-CoV-2 showed 79.6% sequence identity to SARS-CoV, with 96% identity to a bat coronavirus at the whole-genome level. COVID-19 has caused over 133,000 deaths and there are over 2 million total confirmed cases as of April 15th, 2020. Current treatment plans are still under investigation due to a lack of understanding of COVID-19. One potential mechanism to slow disease progression is the use of antiviral drugs to either block the entry of the virus or interfere with viral replication and maturation. Currently, antiviral drugs, including chloroquine/hydroxychloroquine, remdesivir, and lopinavir/ritonavir, have shown effective inhibition of SARS-CoV-2 in vitro. Due to the high dose needed and narrow therapeutic window, many patients are experiencing severe side effects with the above drugs. Hence, repurposing these drugs with a proper formulation is needed to improve the safety and efficacy for COVID-19 treatment. Extracellular vesicles (EVs) are a family of natural carriers in the human body. They play a critical role in cell-to-cell communications. EVs can be used as unique drug carriers to deliver protease inhibitors to treat COVID-19. EVs may provide targeted delivery of protease inhibitors, with fewer systemic side effects. More importantly, EVs are eligible for major aseptic processing and can be upscaled for mass production. Currently, the FDA is facilitating applications to treat COVID-19, which provides a very good chance to use EVs to contribute in this combat.


Subject(s)
Coronavirus Infections/drug therapy , Drug Repositioning , Extracellular Vesicles/chemistry , HIV Protease Inhibitors/administration & dosage , Pneumonia, Viral/drug therapy , Betacoronavirus/genetics , Betacoronavirus/metabolism , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Drug Approval , Drug Delivery Systems , Humans , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS-CoV-2
9.
Pharmaceuticals (Basel) ; 13(3)2020 Mar 21.
Article in English | MEDLINE | ID: covidwho-1725914

ABSTRACT

The COVID-19 coronavirus is currently spreading around the globe with limited treatment options available. This article presents the rationale for potentially using old drugs (emetine, other ipecac alkaloids or analogues) that have been used to treat amoebiasis in the treatment of COVID-19. Emetine had amongst the lowest reported half-maximal effective concentration (EC50) from over 290 agents screened for the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses. While EC50 concentrations of emetine are achievable in the blood, studies show that concentrations of emetine can be almost 300 times higher in the lungs. Furthermore, based on the relative EC50s of emetine towards the coronaviruses compared with Entamoeba histolytica, emetine could be much more effective as an anti-coronavirus agent than it is against amoebiasis. This paper also discusses the known side effects of emetine and related compounds, how those side effects can be managed, and the optimal method of administration for the potential treatment of COVID-19. Given the serious and immediate threat that the COVID-19 coronavirus poses, our long history with emetine and the likely ability of emetine to reach therapeutic concentrations within the lungs, ipecac, emetine, and other analogues should be considered as potential treatment options, especially if in vitro studies confirm viral sensitivity.

10.
Chin Med J (Engl) ; 133(9): 1051-1056, 2020 May 05.
Article in English | MEDLINE | ID: covidwho-1722622

ABSTRACT

BACKGROUND: Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those institutions without such facilities or 2019-nCoV. This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV-related coronavirus model. METHODS: A 2019-nCoV-related pangolin coronavirus GX_P2V/pangolin/2017/Guangxi was described. Whether GX_P2V uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA)-mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2V infection. The anti-viral activities and anti-viral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively. RESULTS: The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs, including cepharanthine (CEP), selamectin, and mefloquine hydrochloride, exhibited complete inhibition of cytopathic effects in cell culture at 10 µmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC50] of 0.98 µmol/L. The viral RNA yield in cells treated with 10 µmol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48 ±â€Š0.02] × 10vs. 1.00 ±â€Š0.12, t = 150.38, P < 0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 µmol/L CEP at 48 h p.i. Furthermore, we found CEP had potent anti-viral activities against both viral entry (0.46 ±â€Š0.12, vs.1.00 ±â€Š0.37, t = 2.42, P < 0.05) and viral replication ([6.18 ±â€Š0.95] × 10vs. 1.00 ±â€Š0.43, t = 3.98, P < 0.05). CONCLUSIONS: Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin, and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and further study of CEP for treatment of 2019-nCoV infection is warranted.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Betacoronavirus/genetics , COVID-19 , COVID-19 Testing , Cell Line , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Drug Approval , Humans , Pandemics , Pneumonia, Viral/diagnosis , RNA, Small Interfering/genetics , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Viral Load
11.
Food Funct ; 11(6): 5565-5572, 2020 Jun 24.
Article in English | MEDLINE | ID: covidwho-1721602

ABSTRACT

To date, no specific drug has been discovered for the treatment of COVID-19 and hence, people are in a state of anxiety. Thus, there is an urgent need to search for various possible strategies including nutritional supplementation. In this study, we have tried to provide a reference for protein supplementation. Specifically, 20 marine fish proteins were subjected to in silico hydrolysis by gastrointestinal enzymes, and a large number of active peptides were generated. Then, the binding abilities of these peptides to SARS-CoV-2 main protease and monoamine oxidase A were assessed. The results showed that NADH dehydrogenase could be a good protein source in generating potent binders to the two enzymes, followed by cytochrome b. In addition, some high-affinity oligopeptides (VIQY, ICIY, PISQF, VISAW, AIPAW, and PVSQF) were identified as dual binders to the two enzymes. In summary, the supplementation of some fish proteins can be helpful for COVID-19 patients; the identified oligopeptides can be used as the lead compounds to design potential inhibitors against COVID-19 and anxiety.


Subject(s)
Antiviral Agents/metabolism , Betacoronavirus/metabolism , Coronavirus Infections/virology , Dietary Supplements , Fish Proteins/metabolism , Monoamine Oxidase/metabolism , Pneumonia, Viral/virology , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Aquatic Organisms , Betacoronavirus/enzymology , COVID-19 , Coronavirus Infections/drug therapy , Decapodiformes/metabolism , Fish Proteins/chemistry , Fish Proteins/therapeutic use , Fishes/metabolism , Models, Molecular , Molecular Docking Simulation , Monoamine Oxidase Inhibitors , Pandemics , Perciformes/metabolism , Pneumonia, Viral/drug therapy , Protein Binding , Protein Conformation , SARS-CoV-2 , Salmon/metabolism , Tuna/metabolism
12.
SN Compr Clin Med ; 2(9): 1436-1443, 2020.
Article in English | MEDLINE | ID: covidwho-1700862

ABSTRACT

The outbreak of a large plaque, novel coronavirus pneumonia (NCP), which also named Coronavirus Disease 2019 (COVID-19) by the WHO, has detrimentally affected the livelihood and health of people in China. During the spread of COVID-19, colleagues who have been working at the frontline have had to face many new challenges in the treatment and prevention of NCP. Therefore, we have provided suggestions for the diagnosis, treatment, and prevention of the novel coronavirus pneumonia in the current epidemic situation based on the latest reports and the experience of doctors treating COVID-19 in our hospital. We recommend lopinavir/ritonavir as the effective drugs for antiviral treatment according to our experience in administering lopinavir/ritonavir to COVID-19 patients and the successful cases of these drugs in treating MERS and SARS, but need more clinical data to prove their efficacy in treating COVID-19.

13.
J Evid Based Integr Med ; 26: 2515690X211020685, 2021.
Article in English | MEDLINE | ID: covidwho-1691167

ABSTRACT

The retrospective cohort study aimed to evaluate the clinical outcomes of Ayurveda treatment exposure as an add-on to conventional care in early stage COVID-19 patients admitted at Samaras COVID care center, Ahmedabad, India. Conventional care included Vitamin-c, Azithromycin, and Paracetamol. Ayurveda formulations used as add-on were Dashamula and Pathyadi decoctions along with Trikatu powder, Sanshamani tablet, AYUSH-64 tablet AND Yastimadhu Ghana tablet for oral administration. Considering Add-on Ayurveda medicines as exposure of interest, patients who received Add-on Ayurveda medicines at least for 7 days were included in the exposed group while those who received only conventional care in unexposed group. Data was collected through record review and telephonic interviews. The outcomes of interest were the development of symptoms, duration of symptomatic phase in those progressing to symptomatic stage and mortality. Total 762 participants were included-[541 (71%) in the exposed group and 221 (29%) in the unexposed. Progression to symptomatic phase did not differ significantly between groups [27.6% in exposed, 24.6% in unexposed, adjusted RR 0.85; 95% CI 0.6-1.2]. The total duration of symptomatic phase among those progressing to the symptomatic stage was significantly decreased in the exposed group (x¯ = 3.66 ± 1.55 days in exposed (n = 133); x¯ = 5.34 ± 3.35 days in unexposed (n = 61), p < 0.001). No mortality was observed in either of the groups. Ayurveda Treatment as adjunctive to conventional care reduced the duration of symptomatic phase in early stage COVID-19 as compared to standalone conventional care. Add-on Ayurveda treatment has promising potential for management of early stage COVID-19.


Subject(s)
Acetaminophen/therapeutic use , COVID-19 , Medicine, Ayurvedic/methods , Plant Extracts/therapeutic use , Plant Preparations/therapeutic use , Antipyretics/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/epidemiology , Complementary Therapies/methods , Drug Therapy, Combination/methods , Female , Hospitalization/statistics & numerical data , Humans , India/epidemiology , Male , Middle Aged , Patient Acuity , Retrospective Studies , SARS-CoV-2/isolation & purification , Treatment Outcome
14.
Netw Model Anal Health Inform Bioinform ; 10(1): 32, 2021.
Article in English | MEDLINE | ID: covidwho-1682163

ABSTRACT

Outbreak of Coronavirus (SARS-CoV-2) has thrown a big challenge to the globe by snatching millions of human lives from the world. In this study, inhibitory efficiency of ten anti-HIV compounds from different Indian medicinal plant parts have been virtually screened against Mpro, PLpro and RdRp proteins of SARS-CoV-2. The molecular docking study reflected that among these compounds, Proptine (PTP) has the highest binding affinity for the three cases. Introduction of PTP molecules within the binding pocket of these proteins showed a large structural and conformational changes on the structure of proteins which is revealed from molecular dynamics (MD) simulation studies. RMSD, RMSF and analysis of thermodynamic parameters also revealed that PTP makes a huge impact on the structures of the respective proteins which will pave an opportunity for doing advanced experimental research to evaluate the potential drug to combat COVID-19. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13721-021-00309-3.

15.
Curr Pharmacol Rep ; 6(5): 228-240, 2020.
Article in English | MEDLINE | ID: covidwho-1682288

ABSTRACT

The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for causing coronavirus disease 2019 (COVID-19), marked the third time in the twenty-first century when a new, highly pathogenic human coronavirus outbreak has led to an epidemic. The COVID-19 epidemic has emerged in late December 2019 in Wuhan city of China and spread rapidly to other parts of the world. This quick spread of SARS-CoV-2 infection to many states across the globe affecting many people has led WHO to declare it a pandemic on March 12, 2020. As of July 4, 2020, more than 523,011 people lost their lives worldwide because of this deadly SARS-CoV-2. The current situation becomes more frightening as no FDA-approved drugs or vaccines are available to treat or prevent SARS-CoV-2 infection. The current therapeutic options for COVID-19 are limited only to supportive measures and non-specific interventions. So, the need of the hour is to search for SARS-CoV-2-specific antiviral treatments and to develop vaccines for SARS-CoV-2. Also, it is equally important to maintain our immunity, and natural products and Ayurvedic medicines are indispensable in this regard. In this review, we discuss recent updates regarding various therapeutic approaches to combat COVID-19 pandemic and enlist the major pipeline drugs and traditional medicines that are under trial for COVID-19. Also, possible mechanisms involved in viral pathogenesis are discussed, which further allow us to understand various drug targets and helps in discovering novel therapeutic approaches for COVID-19. Altogether, the information provided in this review will work as an intellectual groundwork and provides an insight into the ongoing development of various therapeutic agents.

16.
Mini Rev Med Chem ; 22(2): 273-311, 2022.
Article in English | MEDLINE | ID: covidwho-1666892

ABSTRACT

Due to the high mortality rate of the 2019 coronavirus disease (COVID-19) pandemic, there is an immediate need to discover drugs that can help before a vaccine becomes available. Given that the process of producing new drugs is so long, the strategy of repurposing existing drugs is one of the promising options for the urgent treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 disease. Although FDA has approved Remdesivir for the use in hospitalized adults and pediatric patients suffering from COVID-19, no fully effective and reliable drug has been yet identified worldwide to treat COVID-19 specifically. Thus, scientists are still trying to find antivirals specific to COVID-19. This work reviews the chemical structure, metabolic pathway, and mechanism of action of the existing drugs with potential therapeutic applications for COVID-19. Furthermore, we summarized the molecular docking stimulation of the medications related to key protein targets. These already established drugs could be further developed, and after their testing through clinical trials, they could be used as suitable therapeutic options for patients suffering from COVID-19.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/virology , Metabolic Networks and Pathways/drug effects , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , Antiviral Agents/therapeutic use , Humans , Molecular Docking Simulation , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity
17.
Clin Infect Dis ; 74(1): 24-31, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1634311

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has strained healthcare systems with patient hospitalizations and deaths. Anti-spike monoclonal antibodies, including bamlanivimab, have demonstrated reduction in hospitalization rates in clinical trials, yet real-world evidence is lacking. METHODS: We conducted a retrospective case-control study across a single healthcare system of nonhospitalized patients, age 18 years or older, with documented positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, risk factors for severe COVID-19, and referrals for bamlanivimab via emergency use authorization. Cases were defined as patients who received bamlanivimab; contemporary controls had a referral order placed but did not receive bamlanivimab. The primary outcome was 30-day hospitalization rate from initial positive SARS-CoV-2 polymerase chain reaction (PCR). Descriptive statistics, including χ 2 and Mann-Whitney U test, were performed. Multivariable logistic regression was used for adjusted analysis to evaluate independent associations with 30-day hospitalization. RESULTS: Between 30 November 2020 and 19 January 2021, 218 patients received bamlanivimab (cases), and 185 were referred but did not receive drug (controls). Thirty-day hospitalization rate was significantly lower among patients who received bamlanivimab (7.3% vs 20.0%, risk ratio [RR] 0.37, 95% confidence interval [CI]: .21-.64, P < .001), and the number needed to treat was 8. On logistic regression, odds of hospitalization were increased in patients not receiving bamlanivimab and with a higher number of pre-specified comorbidities (odds ratio [OR] 4.19 ,95% CI: 1.31-2.16, P < .001; OR 1.68, 95% CI: 2.12-8.30, P < .001, respectively). CONCLUSIONS: Ambulatory patients with COVID-19 who received bamlanivimab had a lower 30-day hospitalization than control patients in real-world experience. We identified receipt of bamlanivimab and fewer comorbidities as protective factors against hospitalization.Bamlanivimab's role in preventing hospitalization associated with coronavirus disease 2019 (COVID-19) remains unclear. In a real-world, retrospective study of 403 high-risk, ambulatory patients with COVID-19, receipt of bamlanivimab compared to no monoclonal antibody therapy was associated with lower 30-day hospitalization.


Subject(s)
COVID-19 , Adolescent , Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing , Case-Control Studies , Humans , Retrospective Studies , SARS-CoV-2
18.
Clin Infect Dis ; 74(1): 74-82, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1632784

ABSTRACT

BACKGROUND: Trends in prescribing for nursing home (NH) residents, which may have been influenced by the coronavirus disease 2019 (COVID-19) pandemic, have not been characterized. METHODS: Long-term care pharmacy data from 1944 US NHs were used to evaluate trends in prescribing of antibiotics and drugs that were investigated for COVID-19 treatment, including hydroxychloroquine, famotidine, and dexamethasone. To account for seasonal variability in antibiotic prescribing and decreased NH occupancy during the pandemic, monthly prevalence of residents with a prescription dispensed per 1000 residents serviced was calculated from January to October and compared as relative percent change from 2019 to 2020. RESULTS: In April 2020, prescribing was significantly higher in NHs for drugs investigated for COVID-19 treatment than 2019; including hydroxychloroquine (+563%, 95% confidence interval [CI]: 5.87, 7.48) and azithromycin (+150%, 95% CI: 2.37, 2.63). Ceftriaxone prescribing also increased (+43%, 95% CI: 1.34, 1.54). Prescribing of dexamethasone was 36% lower in April (95% CI: .55, .73) and 303% higher in July (95% CI: 3.66, 4.45). Although azithromycin and ceftriaxone prescribing increased, total antibiotic prescribing among residents was lower from May (-5%, 95% CI: .94, .97) through October (-4%, 95% CI: .94, .97) in 2020 compared to 2019. CONCLUSIONS: During the pandemic, large numbers of residents were prescribed drugs investigated for COVID-19 treatment, and an increase in prescribing of antibiotics commonly used for respiratory infections was observed. Prescribing of these drugs may increase the risk of adverse events, without providing clear benefits. Surveillance of NH prescribing practices is critical to evaluate concordance with guideline-recommended therapy and improve resident safety.


Subject(s)
COVID-19 , Pharmaceutical Preparations , Anti-Bacterial Agents/therapeutic use , COVID-19/drug therapy , Humans , Nursing Homes , Pandemics , SARS-CoV-2
19.
Infect Disord Drug Targets ; 21(8): e160921189190, 2021.
Article in English | MEDLINE | ID: covidwho-1625155

ABSTRACT

Coronavirus Disease (COVID-19) pandemic has affected more than seven million individuals in 213 countries worldwide with a basic reproduction number ranging from 1.5 to 3.5 and an estimated case fatality rate ranging from 2% to 7%. A substantial proportion of COVID-19 patients are asymptomatic; however, symptomatic cases might present with fever, cough, and dyspnoea or severe symptoms up to acute respiratory distress syndrome. Currently, RNA RT-PCR is the screening tool, while bilateral chest CT is the confirmatory clinical diagnostic test. Several drugs have been repurposed to treat COVID-19, including chloroquine or hydroxychloroquine with or without azithromycin, lopinavir/ritonavir combination, remdesivir, favipiravir, tocilizumab, and EIDD-1931. Recently, Remdesivir gained FDA emergency approval based on promising early findings from the interim analysis of 1063 patients. The recently developed serology testing for SARSCoV-2 antibodies opened the door to evaluate the actual burden of the disease and to determine the rate of the population who have been previously infected (or developed immunity). This review article summarizes current data on the COVID-19 pandemic starting from the early outbreak, viral structure and origin, pathogenesis, diagnosis, treatment, discharge criteria, and future research.


Subject(s)
COVID-19 , Pandemics , Antiviral Agents/therapeutic use , Diagnostic Tests, Routine , Humans , SARS-CoV-2
20.
Am J Epidemiol ; 190(8): 1452-1456, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1585169

ABSTRACT

The coronavirus disease 2019 pandemic, which was caused by the severe acute respiratory syndrome coronavirus 2, has led to an unprecedented effort to generate real-world evidence on the safety and effectiveness of various treatments. A growing number of observational studies in which the effects of certain drugs were evaluated have been conducted, including several in which researchers assessed whether hydroxychloroquine improved outcomes in infected individuals and whether renin-angiotensin-aldosterone system inhibitors have detrimental effects. In the present article, we review and illustrate how immortal time bias and selection bias were present in several of these studies. Understanding these biases and how they can be avoided may prove important for future observational studies assessing the effectiveness and safety of potentially promising drugs during the coronavirus 19 pandemic.


Subject(s)
COVID-19/drug therapy , Cohort Studies , Drug Evaluation/methods , Randomized Controlled Trials as Topic , Bias , Humans , Research Design , SARS-CoV-2
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