Single-centre review of rapid antiretroviral therapy initiation during the COVID-19 pandemic

Background: BHIVA released interim guidance on first line anti-retroviral therapy (ART) initiation during the COVID-19 pandemic, when investigations/follow-up was restricted. Our HIV service didn't restrict follow-up but suspended in-house resistance testing (RT) due to laboratory capacity. Having prescribed 'rapid ART' based on the Northern Algorithm 01/08/2020-01/01/2022 we wanted to evaluate our prescribing during the pandemic. Method(s): All new HIV diagnoses 01/08/2020-31/12/2021 were identified via our HARS dataset. Retrospective casenote review identified ART prescribed, and switches that occurred upon baseline RT availability, to more suitable and/or cost-effective regimes. Result(s): 32 new diagnoses: 11 female, 21 male, median age 41 years (17-81), 10 MSM, 22 Heterosexuals, White British 14, African 9, other 7. Median time to ART initiation 10 days (0-210). Median CD4 count 359 (2-1251), 8 had CD4<200. 7/32 had Primary HIV infection, 5 initiating ART at 1st visit. 30/32 started ART within our service, 1 relocated, 1 initiated abroad. 28/30 started algorithm compliant rapid ART. Of the 2 that delayed, 1 had significant resistance, the other patient choice. 8/30 (27%) 'rapid ART' initiations switched post RT availability. Conclusion(s): All patients initiating ART in our service during the pandemic were algorithm compliant and fulfilled BHIVA recommendations. 7/10 starting Darunavir/ r-based therapy switched to Delstrigo post RT, a more cost-effective STR. Zero patients on Biktarvy switched post RT;implying it's difficult to switch patients from small INSTI-based-STRs. Future work includes comparing our results with other centres and reviewing ART switches post HIV National Prescribing Guide implementation. (Table Presented).

Darunavir ethanolate: Repurposing an anti-HIV drug in COVID-19 treatment.

Antivirals already on the market and expertise gained from the SARS and MERS outbreaks are gaining momentum as the most effective way to combat the coronavirus outbreak. SARS-CoV-2 has caused considerable mortality due to respiratory failure, highlighting the immediate need for successful therapies as well as the long-term need for antivirals to combat potential emergent mutants of coronaviruses. There are constant viral mutations are being observed due to which world is experiencing different waves of SARS-CoV-2. If our understanding of the virology and clinical presentation of COVID-19 grows, so does the pool of possible pharmacological targets. In COVID-19, the difficulties of proper analysis of current pre-clinical/clinical data as well as the creation of new evidence concerning drug repurposing will be crucial. The current manuscript aims to evaluate the repurposing of an anti-HIV drug Darunavir Ethanolate in COVID-19 treatment with in silico study and we discuss the therapeutic progress of Darunavir Etanolate, to prevent SARS-CoV-2 replication, which supports its clinical assessment for COVID-19 therapy.

Effect of low-to-moderate dose glucocorticoids on viral clearance in COVID-19: a retrospective study.

Objective: To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance in patients with COVID-19. Methods: A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, Zhejiang University School of Medicine were recruited. All patients received oral arbidol and combination of lopinavir/ritonavir or darunavir/cobistitat for antiviral therapy, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg.kg-1.d-1) (glucocorticoid treatment group), and 21 patients did not use glucocorticoid (control group). The time of virologic negative conversion in sputum and the time of radiologic recovery in lung since onset were compared between the two groups. The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results: The median ages of the glucocorticoid group and the control group were 52 (45, 62) and 46 (32, 56) years (chi2=4.365, P<0.05). The clinical conditions at hospital admission were different between the two groups (P<0.01). The severe cases accounted for 52.0%, while moderate cases in the control group accounted for 71.4%. The median times from the onset to virologic negative conversion in the two groups were 15 (13, 20) and 14 (12, 20) days (P>0.05). The median times from onset to radiologic recovery were 13 (11, 15) and 13 (12, 17) days in the two groups (P>0.05). In moderate cases, the median times from the onset to virologic conversion in sputum were 13 (11, 18) days in the glucocorticoid group and 13 (12, 15) days in the control group (P>0.05). The median times from onset to radiologic recovery in lung were 12 (10, 15) and 13 (12, 17) days, respectively (P>0.05). Conclusion(s): Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19, and also no effect on accelerating radiologic recovery in lung, so it is not recommended.Copyright © 2020 by the Chinese Medical Association.

Effect of low-to-moderate dose glucocorticoids on viral clearance in COVID-19: a retrospective study.

Objective: To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance in patients with COVID-19. Methods: A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, Zhejiang University School of Medicine were recruited. All patients received oral arbidol and combination of lopinavir/ritonavir or darunavir/cobistitat for antiviral therapy, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg.kg-1.d-1) (glucocorticoid treatment group), and 21 patients did not use glucocorticoid (control group). The time of virologic negative conversion in sputum and the time of radiologic recovery in lung since onset were compared between the two groups. The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results: The median ages of the glucocorticoid group and the control group were 52 (45, 62) and 46 (32, 56) years (chi2=4.365, P<0.05). The clinical conditions at hospital admission were different between the two groups (P<0.01). The severe cases accounted for 52.0%, while moderate cases in the control group accounted for 71.4%. The median times from the onset to virologic negative conversion in the two groups were 15 (13, 20) and 14 (12, 20) days (P>0.05). The median times from onset to radiologic recovery were 13 (11, 15) and 13 (12, 17) days in the two groups (P>0.05). In moderate cases, the median times from the onset to virologic conversion in sputum were 13 (11, 18) days in the glucocorticoid group and 13 (12, 15) days in the control group (P>0.05). The median times from onset to radiologic recovery in lung were 12 (10, 15) and 13 (12, 17) days, respectively (P>0.05). Conclusion(s): Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19, and also no effect on accelerating radiologic recovery in lung, so it is not recommended.Copyright © 2020 by the Chinese Medical Association.

Effect of low-to-moderate dose glucocorticoids on viral clearance in COVID-19: a retrospective study.

Objective: To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance in patients with COVID-19. Methods: A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, Zhejiang University School of Medicine were recruited. All patients received oral arbidol and combination of lopinavir/ritonavir or darunavir/cobistitat for antiviral therapy, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg.kg-1.d-1) (glucocorticoid treatment group), and 21 patients did not use glucocorticoid (control group). The time of virologic negative conversion in sputum and the time of radiologic recovery in lung since onset were compared between the two groups. The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results: The median ages of the glucocorticoid group and the control group were 52 (45, 62) and 46 (32, 56) years (chi2=4.365, P<0.05). The clinical conditions at hospital admission were different between the two groups (P<0.01). The severe cases accounted for 52.0%, while moderate cases in the control group accounted for 71.4%. The median times from the onset to virologic negative conversion in the two groups were 15 (13, 20) and 14 (12, 20) days (P>0.05). The median times from onset to radiologic recovery were 13 (11, 15) and 13 (12, 17) days in the two groups (P>0.05). In moderate cases, the median times from the onset to virologic conversion in sputum were 13 (11, 18) days in the glucocorticoid group and 13 (12, 15) days in the control group (P>0.05). The median times from onset to radiologic recovery in lung were 12 (10, 15) and 13 (12, 17) days, respectively (P>0.05). Conclusion(s): Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19, and also no effect on accelerating radiologic recovery in lung, so it is not recommended.Copyright © 2020 by the Chinese Medical Association.

Progress on cross-species infection mechanism of 2019-nCoV and antiviral drug research.

2019-nCoV has a up to 96% homology with the gene sequence of a bat coronavirus. By comparing its 7 conserved non-structural proteins, it is found that 2019-nCoV belongs to SARS related coronaviruses(SARSr-CoV). The receptor for 2019-nCoV entering cells is the same as that for SARSr-CoV, and angiotensin-converting enzyme 2 (ACE2) is a common cross-genus receptor. This article first elaborates the interspecies transmission and genetic variation, then briefly discusses the receptors on the surface of human cells (such as ACE2 and APP4), which cause human infection and encode five proteins in the viral genome, therefore are important targets for development of antiviral drugs. The article reviews eight promising anti-coronavirus drugs, including three anti-HIV drugs (Lopinavir/Ritonavir, Danoprevir/Ritonavir, Darunavir), two anti-Ebola virus drugs (Remdesivir, Galidesivir), two anti-influenza virus drugs (Arbidol, Favipiravir) and one anti-malarial drug (chloroquine phosphate). Among them, Remdesivir, Abidol and Favipiravir have strong inhibitory effects on 2019-nCoV, they may be the most promising drugs under investigation.Copyright © 2020 by the Chinese Medical Association.

Progress on cross-species infection mechanism of 2019-nCoV and antiviral drug research.

2019-nCoV has a up to 96% homology with the gene sequence of a bat coronavirus. By comparing its 7 conserved non-structural proteins, it is found that 2019-nCoV belongs to SARS related coronaviruses(SARSr-CoV). The receptor for 2019-nCoV entering cells is the same as that for SARSr-CoV, and angiotensin-converting enzyme 2 (ACE2) is a common cross-genus receptor. This article first elaborates the interspecies transmission and genetic variation, then briefly discusses the receptors on the surface of human cells (such as ACE2 and APP4), which cause human infection and encode five proteins in the viral genome, therefore are important targets for development of antiviral drugs. The article reviews eight promising anti-coronavirus drugs, including three anti-HIV drugs (Lopinavir/Ritonavir, Danoprevir/Ritonavir, Darunavir), two anti-Ebola virus drugs (Remdesivir, Galidesivir), two anti-influenza virus drugs (Arbidol, Favipiravir) and one anti-malarial drug (chloroquine phosphate). Among them, Remdesivir, Abidol and Favipiravir have strong inhibitory effects on 2019-nCoV, they may be the most promising drugs under investigation.Copyright © 2020 by the Chinese Medical Association.

Progress on cross-species infection mechanism of 2019-nCoV and antiviral drug research.

2019-nCoV has a up to 96% homology with the gene sequence of a bat coronavirus. By comparing its 7 conserved non-structural proteins, it is found that 2019-nCoV belongs to SARS related coronaviruses(SARSr-CoV). The receptor for 2019-nCoV entering cells is the same as that for SARSr-CoV, and angiotensin-converting enzyme 2 (ACE2) is a common cross-genus receptor. This article first elaborates the interspecies transmission and genetic variation, then briefly discusses the receptors on the surface of human cells (such as ACE2 and APP4), which cause human infection and encode five proteins in the viral genome, therefore are important targets for development of antiviral drugs. The article reviews eight promising anti-coronavirus drugs, including three anti-HIV drugs (Lopinavir/Ritonavir, Danoprevir/Ritonavir, Darunavir), two anti-Ebola virus drugs (Remdesivir, Galidesivir), two anti-influenza virus drugs (Arbidol, Favipiravir) and one anti-malarial drug (chloroquine phosphate). Among them, Remdesivir, Abidol and Favipiravir have strong inhibitory effects on 2019-nCoV, they may be the most promising drugs under investigation.Copyright © 2020 by the Chinese Medical Association.

Knowledge, Concept on severe Acute Respiratory Syndrome Coronavirus-2(SARS-CoV-2). A Review of the Literature and Future perspective

Severe acute respiratory corona virus-2 (SARS-CoV-2) is a newly recognized pathogen and may cause severe respiratory illness among virus-infected people. The virus in the open market of Wuhan city, China was identified. The virus causative agent for the COVID-19 disease and became pandemic in December 2019 to now with no proper disease management protocols. So, the authors felt a need to bring awareness to the disease and its causative agent among worldwide.The current review article is trying to bringglance information on SARS-CoV-2 on various aspects of disease condition as Common characteristics, history, and mode of transmissions of the virus. The virus can be detected through investigations, Identified clinical manifestations for the virus, and available management used to treat the virus-infected patient. Here discussed possible preventive measures for SARS-CoV-2;to control the spread of the disease among the communities. This article information maybea help people to have an awareness of the disease.Health professional are trying hard for providing effective care to the virus affected people with minimal disease preventive protocols. People should understand the effectiveness of the vaccine and undergoing vaccination process which helps the spread of virus among the healthy people. Every individual should take initiation for the control of the disease spreads by following controlling measures.Copyright © RJPT All right reserved.

COVID-19: From the Molecular Mechanisms to Treatment

The 2019 novel coronavirus (SARS-CoV-2) causes severe pneumonia called COVID-19 and leads to severe acute respiratory syndrome with a high mortality rate. The SARS-CoV-2 virus in the human body leads to jumpstarting immune reactions and multi-organ inflammation, which has poorer outcomes in the presence of predisposing conditions, including hypertension, dyslipidemia, dysglycemia, abnormal adiposity, and even endothelial dysfunction via biomolecular mechanisms. In addition, leucopenia, hypoxemia, and high levels of both cytokines and chemokines in the acute phase of this disease, as well as some abnormalities in chest CT images, were reported in most patients. The spike protein in SARS-CoV-2, the primary cell surface protein, helps the virus anchor and enter the human host cells. Additionally, new mutations have mainly happened for spike protein, which has promoted the infection's transmissibility and severity, which may influence manufactured vaccines' efficacy. The exact mechanisms of the pathogenesis, besides molecular aspects of COVID-19 related to the disease stages, are not well known. The altered molecular functions in the case of immune responses, including T CD4+, CD8+, and NK cells, besides the overactivity in other components and outstanding factors in cytokines like interleukin-2, were involved in severe cases of SARS-CoV-2. Accordingly, it is highly needed to identify the SARS-CoV-2 bio-molecular characteristics to help identify the pathogenesis of COVID-19. This study aimed to investigate the bio-molecular aspects of SARS-CoV-2 infection, focusing on novel SARS-CoV-2 variants and their effects on vaccine efficacy.Copyright © 2022 NRITLD, National Research Institute of Tuberculosis and Lung Disease, Iran.

Pathogenesis, Clinical Manifestation, Diagnosis, Pathological Findings, Treatment Options, Preventive Measures, and Risk Factors of COVID-19

Background: COVID-19 is an infectious disease caused by SARS-CoV-2. The disease has hit hard around the globe and is now a pandemic. As of April 01, 2020, a total of 875,560 cases have been reported and the figures are increasing day by day. Currently, there is no treatment or vaccine available for curing COVID-19 and pharmaceutical companies are racing toward the common goal of achieving the cure. Method(s): Scientific databases, including Science direct, Pub med, Elsevier, Scopus, and Nature, were explored. Data has also been accessed from case reports, newspaper reports, internet data, World Health Organisation (WHO) reports, and Centre of Disease Control (CDCs) reports. The US National Library of Medicine, Clinicaltrials.gov, were accessed to get information about the ongoing clinical trials. The literature survey started in the first week of February 2020 and was completed in the first week of April 2020. Additional literature survey was done in the second week of June 2020. Result(s): The epicentre of COVID-19 is Wuhan City, Hubei Province, China. Coronavirus belongs to Order Nidovirale and is subdivided into four groups alpha, beta, gamma, and delta. Coronavirus 229E, NL63, HKU1, MERS-CoV and SARS-CoV are known to infect humans. It is an enveloped, non-segmented positive-sense RNA virus of size 30-32 kb with several structural and accessory proteins. The pathogenesis of COVID-19 involves attachment of Spike (S) protein of SARS-CoV-2 to the angio-tensin-converting enzyme 2(ACE2) receptor present on the host cell membrane. Clinical manifestation of COVID-19 include fever, cough, complicated dyspnoea, pneumonia, etc. Real-time-PCR is a sensi-tive test for the detection of SARS-CoV. Remdesivir, Bevacizumab, Darunavir and cobicistat, lopinavir-ritonavir, Oseltamavir, hydroxychloroquine, Sarilumab, mRNA-1273, Ad5-nCoV are some of the drugs under the clinical phase of the trial. People with A-positive blood group, with comorbidities like diabe-tes, hypertension, chronic pulmonary obstructive disease, substance abuse disorders, immunocom-promised individuals, health care workers, and older adults are at high risk of getting infected with SARS-CoV-2 Conclusion(s): This article gives insight into the occurrence of COVID-19, classification and structure of SARS-CoV-2, pathogenesis, pathological findings, clinical manifestation, diagnosis, potential treatment options and prevention, and people at risk of COVID-19.Copyright © 2021 Bentham Science Publishers.

Liver injury caused by antiviral agents for COVID-19.

Antiviral therapy is important for COVID-19. Currently, the anti-2019-nCoV drugs in clinical trials include broad-spectrum antiviral drugs (alpha interferon and ribavirin), hemagglutinin inhibitors (arbidol), human immunodeficiency virus protease inhibitors (lopinavir/ritonavir and darunavir/cobicistat), nucleoside analogues (favipiravir and remdesivir) and antimalarial drug (chloroquine);while liver damage may occur in some patients with the medication. This article reviews the research on liver damage associated with anti-2019-nCoV drugs, aiming at promoting the safe and effective antiviral therapy for COVID-19 patients.Copyright © 2020 by the Chinese Medical Association.

Liver injury caused by antiviral agents for COVID-19.

Antiviral therapy is important for COVID-19. Currently, the anti-2019-nCoV drugs in clinical trials include broad-spectrum antiviral drugs (alpha interferon and ribavirin), hemagglutinin inhibitors (arbidol), human immunodeficiency virus protease inhibitors (lopinavir/ritonavir and darunavir/cobicistat), nucleoside analogues (favipiravir and remdesivir) and antimalarial drug (chloroquine);while liver damage may occur in some patients with the medication. This article reviews the research on liver damage associated with anti-2019-nCoV drugs, aiming at promoting the safe and effective antiviral therapy for COVID-19 patients.Copyright © 2020 by the Chinese Medical Association.

COVID-19 Infection: A Review of Summarized Clinical Trials Study for the Treatment

Background: Coronavirus Disease 2019 (COVID-19) is a widely infectious and pathogenic viral infection. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was reported in Wu-han, China, and spread throughout the world. Coronavirus is indeed an enveloped RNA virus of the ge-nus Betacoronavirus, which is transmitted to birds, humans as well as other mammals. The fastest human to human transition has been generally established. On July 19, 2020, the WHO has reported total confirmed cases: 1,40, 43,176, total confirmed new cases: 1,66,735, total deaths: 5,97,583, and total new deaths: 4,496 globally. Material(s) and Method(s): In this review, the Clinical trial database is analyzed and systematically summarized drugs which are in the recruiting phase and the completion phase of the clinical trial. Result(s): Total 383 clinical trials are listed, involving more than 350 medicines such as Deferoxamine, Favipiravir, DAS181, Tocilizumab Injection, Sarilumab, Placebo, Sildenafil citrate tablets, Sargramo-stim, Lopinavir/ritonavir, Remdesivir, Bevacizumab, Tetrandrine, Fingolimod, Methylprednisolone, Plaquenil, Tocilizumab, Hydroxychloroquine, Abidol hydrochloride, Bevacizumab Injection, Methyl-prednisolone, Amoxicillin-clavulanate, Moxifloxacin, Sarilumab, Darunavir, Cobicistat, etc. Conclusion(s): There is no commercially authorized antiviral treatment or vaccine suitable for use against COVID-19. However, clinical trials represent an effective approach because they facilitate the development of new types of pharmaceutical drugs.Copyright © 2021 Bentham Science Publishers.

O Impacto Da Pandemia De Covid-19 No Atendimento Do Paciente Com Leucemia

Objetivo: Analisar comparativamente as caracteristicas relativas aos gastos destinados a saude para tratamento de pacientes internados por Leucemias antes, durante e apos a pandemia de COVID-19 no Piaui. Materiais e Metodos: O estudo ecologico, de carater descritivo e retrospectivo. Os dados utilizados foram obtidos mediante o Departamento de Informatica do Sistema Unico de Saude (DATASUS), em que foi analisado o perfil de internacoes ocasionadas por leucemias, os gastos empreendidos com esses pacientes, o tempo medio de permanencia, a quantidade total de internacoes e o numero de obitos no periodo de janeiro de 2019 a maio de 2022. Os dados foram agrupados no Microsoft Excel, realizada analise estatistica descritiva, frequencia absoluta e relativa. Resultados: Durante a pandemia, houve reducao de 14,6% no numero de internacoes (779 em 2019 e 665 em 2020) e de 35,5% no valor total gasto com pacientes portadores de Leucemia no estado do Piaui (R$ 2.287.368,42 em 2019 e R$ 1.476.495,97 em 2020). A tendencia foi seguida nos anos de 2021 e 2022 (R$ 1.367.601,50 em 2021 e R$ 611.316,64 ate maio 2022). A media de permanencia em 2019 foi de 8,6 dias, enquanto no periodo de pandemico e pos-pandemico reduziu para 8 dias. O numero de obitos tambem obteve queda de 34,3% quando comparado ao ano anterior da pandemia de COVID-19 (67 obitos em 2019 e 44 obitos em 2020). Discussao: As leucemias compoem um grupo heterogeneo de neoplasias hematologicas resultantes da transformacao total ou parcial das celulas blasticas. Essa doenca tem o carater de alta prevalencia e taxa de mortalidade consideravel, tornando-se imprescindivel tomar estrategias a fim de assegurar a deteccao precoce, que e obtido com a associacao do diagnostico precoce com o rastreamento, segundo a organizacao mundial de saude. O diagnostico precoce acontece quando se tem profissionais bem treinados e uma populacao bem-informada acerca dos sinais e sintomas das leucemias e com acesso garantido as unidades de saude, enquanto o rastreio e uma busca ativa entre um grupo especifico de pessoas que tem maiores chances de virem a desenvolver. Durante a pandemia essa deteccao precoce foi prejudicada e, contrariando as estatisticas, os numeros de novos casos diminuiu, consequencia do foco das campanhas e da deteccao precoce ter sido direcionado ao COVID-19, sugerindo tambem subnotificacoes, os numeros de internacoes caiu, consequencia da falta de leitos, que eram destinados aos pacientes com sindromes respiratorias no periodo de 2020. A queda nos gastos tambem e consequencia da propria diminuicao das internacoes, mas tambem das verbas para saude publica terem sido mais direcionadas para dar suporte ao tratamento dos pacientes com COVID-19. Isso pode ser inferido atraves da analise de custo medio por paciente. Por fim, a queda do numero de obitos tambem foi alta, mas se manteve inalterada entre 2020 e 2021, o que sugere falta de autopsia e ate subnotificacao e notificacoes erroneas, tendo em vista que pacientes leucemicos sao mais propensos a infeccoes, como a propria COVID. Infere-se que os pacientes leucemicos do Piaui tenham ido a obito e notificados como por COVID ou procurado assistencia em maiores polos de saude em outros estados. Conclusao: Apos a analise comparativa dos dados coletados, pode-se concluir que houve uma diminuicao significativa, tanto na quantidade e tempo medio de internacoes e na mortalidade, quanto nos gastos para cuidar desses pacientes. Copyright © 2022

Development of Potent SARS-CoV 3CL Protease Inhibitors: In silico Analogues Designing of Darunavir, Molecular Modelling and Molecular Dynamic Simulation

COVID pandemic initiated in early 2019 and the origin from where it initiated was Wuhan city of China. It changed the whole world. A huge population died due to COVID-19 in spite of taking precautions. New treatments and vaccines are introduced for the treatment and prevention. Among successful treatments, antivirals were found effective against COVID-19. But there is a need to find derivatives, which could be more effective for the treatment of COVID-19. The current research is focused on computational studies on one of the antiviral, darunavir. A computational strategy, molecular docking and molecular dynamic simulation techniques is presented to discover the potent analogues of darunavir for inhibiting protease 3CLpro of SARS-CoV2. The newly discovered X-ray structure (PDB ID: 6LU7) was selected for docking study and generated analogues were docked. The docking results showed that the compounds were bound in the active site of receptor with good binding affinity. It was concluded that compounds D8 and D15 were have good binding affinity value of -9.85 and -8.95 kcal/mol, respectively and these compounds were selected for molecular dynamic simulation (MDS) study to check their stability in pocket of receptor. © 2022 Chemical Publishing Co.. All rights reserved.

A Randomized Controlled Trial of Combined Ivermectin and Zinc Sulfate versus Combined Hydroxychloroquine, Darunavir/Ritonavir, and Zinc Sulfate among Adult Patients with Asymptomatic or Mild Coronavirus-19 Infection.

Introduction: Ivermectin, hydroxychloroquine (HQ), and darunavir/ritonavir are widely prescribed as an oral treatment for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection despite their uncertainty of clinical benefit. The objective is to determine the safety and the efficacies of two treatment regimens against SARS-CoV-2 infection. Methods: We conducted an open-labeled, randomized, controlled trial to compare the efficacy between a 3-day course of once-daily high-dose oral ivermectin plus zinc sulfate (Group A) and a combination of HQ, darunavir/ritonavir, and zinc sulfate (HQ + antiretroviral, Group B) for 5 days in asymptomatic or mild SARS-CoV-2 infection. The study period was between December 2020 and April 2021. Results: Overall, 113 patients were randomized and analyzed (57 patients in Group A and 56 patients in Group B). The median duration to achieve the virological outcome of either undetected or cycle threshold (Ct) for N gene of SARS-CoV-2 by real-time polymerase chain reaction was 6 days (95% confidence interval [CI] 5.3-6.7) versus 7 days (95% CI: 5.4-8.6) in Group A and Group B, respectively (P = 0.419) in the modified intention-to-treat population. All patients were discharged from hospital quarantine as planned. Two patients in Group A and one patient in Group B were considered clinically worsening and received 10 days of favipiravir treatment. There was no serious adverse event found in both groups. Conclusion: We demonstrated that both treatment regimens were safe, but both treatment regimens had no virological or clinical benefit. Based on this result and current data, there is no supporting evidence for the clinical benefit of ivermectin for coronavirus-19.

Computational Intelligence in Identification of Some FDA Approved Drug Compounds for Treatment of COVID-19

Due to unavailability of FDA approved drug for COVID-19, pursuing of available drugs are highlighted to stop COVID-19. Insilico investigation by molecular docking and molecular dynamics simulation help to identify some FDA pre-approved drugs which have a therapeutic effect on SARS-CoV-2. In this study, four drug compounds have been identified by descriptor properties, molecular docking, and molecular dynamics simulation. Between them, Darunavir appeared as the best drug molecule to inhibit the 3C like main protease of SARS-CoV-2. It showed −9.1 kcal/mol binding energy in molecular docking with 3C like main protease of SARS-CoV-2. This study also enlightens on the theory “one molecule, multiple targets”. Multiple target protein was docked by every single drug compound, to check their high therapeutic effect. Molecular dynamics simulations indicate the stable binding of drugs with the target protein. Until the approval of any drug for COVID-19, Darunavir might use as an anti-covid drug. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

SARS-CoV-2 Infection-Of Music and Mechanics of Its Spikes! A Perspective.

The COVID-19 pandemic has been inflicted upon humanity by the SARS-CoV-2 virus, the latest insidious incarnation of the coronaviruses group. While in its wake intense scientific research has produced breakthrough vaccines and cures, there still exists an immediate need to further understand the origin, mechanobiology and biochemistry, and destiny of this virus so that future pandemics arising from similar coronaviruses may be contained more effectively. In this Perspective, we discuss the various evidential findings of virus propagation and connect them to respective underpinning cellular biomechanical states leading to corresponding manifestations of the viral activity. We further propose avenues to tackle the virus, including from a "musical" vantage point, and contain its relentless strides that are currently afflicting the global populace.

COVID-19 AND DERMATOLOGY (PART II): ADVERSE MUCOCUTANEOUS REACTIONS TO MEDICATIONS AND VACCINES USED FOR COVID-19 INFECTION

Background/Aim: There is no proven specific or effective treatment for COVID-19 infection;therefore, many drugs are used empirically to establish control of the infection. Viral infection creates an immunologic environment and facilitate drug sensitization. With the advent of new vaccines, the future holds promise for optimism in establishing control of the pandemic. However, even vaccines are not devoid of side effects. In part II of these review series, we aimed to review the published data on mucocutaneous reactions induced by medications used for COVID-19 infection and vaccines used for COVID-19 prophylaxis. Materials and methods: Literature search was performed in the databases PubMed, Scopus, and Web of Science for the relevant studies, starting from the beginning of COVID-19 pandemic until October 2021. Research on animals, studies utilizing in vitro techniques and publications irrelevant to the study’s framework were excluded. Results: The mucocutaneous side effects liable to medications (antimalarials, azithromycin, lopinavir/ritonavir, remdesivir, ribavirin/interferon, oseltamivir/favipiravir, darunavir, imatinib, tocilizumab, anakinra baricitinib, and other Janus kinase inhibitors, immunoglobulin therapy, colchicine, anti-TNF-α biologics, low molecular weight heparins, camostat mesylate) and vaccines used for COVID-19 infection are reviewed herein. Conclusion: There is a great amount of accumulated data regarding the mucocutaneous side effects of drugs and vaccines used for COVID-19 infection. In the pandemic era, it is a major goal to diagnose drug or vaccine-related mucocutaneous eruptions and distinguish them from pathognomonic, specific, or SARS-CoV-2 virus-related cutaneous eruptions. Timely diagnosis of a mucocutaneous drug/ vaccine reaction will allow for identification of the culprit and appropriate management and protect the patient from forthcoming severe drug/ vaccine reactions. Therefore, it is essential for physicians to update their knowledge regularly on mucocutaneous side effects of COVID-19 therapeutics and vaccines.