Effect of Hydroxychloroquine, Favipiravir, Lopinavir/Ritonavir, Remdesivir, Umifenovir, and Interferon beta-1a in Covid-19 patients: A systematic review of Randomized Clinical Trials

Background: Coronavirus disease 2019 (COVID-19) was recognized by the World Health Organization (WHO) as a global pandemic on March 11, 2020. Since then, researchers worldwide have focused their attention on identifying effective treatments and developing vaccines to combat this disease. Aim: To report the effectiveness of the drugs employed in the COVID-19 treatment protocols based on data from clinical trial studies conducted from the beginning of the pandemic until December 10, 2020. Methods: Following the PRISMA guidelines, we conducted an advanced search in several electronic databases. A total of 13553 studies was screened by two people simultaneously and separately based on the article title, and full-text. The quality of the studies was evaluated using the Cochrane criteria. Results: Of the 13553 studies identified, 50 clinical trials were included in this systematic review. Of these, three studies explored the use of remdesivir, nine studies the use of hydroxychloroquine, five studies the use of lopinavir/ritonavir, six studies the use of favipiravir, one study the use of tocilizumab, two studies the use of interferon beta-1a and two studies the use of umifenovir.

Early antiviral therapy of abidol combined with lopinavir/ritonavir and recombinant interferon alpha-2b for patients with COVID-19 in Zhejiang: A multicenter prospective study.

Objective: To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon alpha-2b (rIFNalpha-2b) and the combination of lopinavir/ritonavir plus rIFNalpha-2b for patients with COVID-19 in Zhejiang province. Method(s): A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNalpha-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data. Result(s): The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2+/-4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0+/-5.0) d] (t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] (H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively (Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8+/-3.9), (13.5+/-5.1) and (11.2+/-4.3) d, respectively(Z=6.722, P<0.05). Conclusion(s): The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNalpha-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy;and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.Copyright © 2020 by the Chinese Medical Association.

Quantitative structure analysis of some molecules in drugs used in the treatment of COVID-19 with topological indices

COVID-19 is a disease caused by the new coronavirus, which has been spreading rapidly all over the world. There is no exact drug yet for the treatment of COVID-19 disease, and its treatment is tried to be provided with existing drugs. However, new drug research is being carried out to treat this disease. Topological indices are numerical descriptors based on the molecular graph of the molecular structure. Topological indices are used in modeling to predict the physicochemical properties and biological activities of molecules in the quantitative structure-property relationship (QSPR), quantitative structure-activity relationship (QSAR) studies. In this study, remdesivir, chloroquine, hydroxychloroquine, theaflavin, thalidomide, arbidol, lopinavir, ritonavir drugs used in the treatment of COVID-19 patients are studied. The QSPR model is designed using some degree-based indices, Mostar-type indices, and distance-based topological indices to predict the various physicochemical properties of these drugs. The relationship analyses between the physicochemical properties and the topological indices in the QSPR model are done by using the curvilinear regression method.

Early antiviral therapy of abidol combined with lopinavir/ritonavir and recombinant interferon alpha-2b for patients with COVID-19 in Zhejiang: A multicenter prospective study.

Objective: To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon alpha-2b (rIFNalpha-2b) and the combination of lopinavir/ritonavir plus rIFNalpha-2b for patients with COVID-19 in Zhejiang province. Method(s): A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNalpha-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data. Result(s): The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2+/-4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0+/-5.0) d] (t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] (H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively (Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8+/-3.9), (13.5+/-5.1) and (11.2+/-4.3) d, respectively(Z=6.722, P<0.05). Conclusion(s): The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNalpha-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy;and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.Copyright © 2020 by the Chinese Medical Association.

A Narrative Review of Emerging Therapeutics for COVID-19.

The novel severe acute respiratory syndrome coronavirus 2, the causal agent of coronavirus disease 2019 (COVID-19), quickly spread around the world, resulting in the most aggressive pandemic experienced in more than 100 years. Research on targeted therapies and vaccines has been initiated on an unprecedented scale and speed but will take months and even years to come to fruition. Meanwhile, the efficacy of emerging therapeutics for use in treating COVID-19 is feverishly being investigated to identify the best available treatment options for dealing with the current wave of disease. This review of publications with a "treatment" tag through June 29, 2020 in the National Library of Medicine's LitCovid literature hub, provides frontline clinicians with a pragmatic summary of the current state of the rapidly evolving evidence supporting emerging candidate therapeutics for COVID-19. Two main categories of pharmaceutical therapeutics are showing promise: those with antiviral activity directly addressing infection and those that counteract the inflammatory cytokine storm induced by severe disease. Preliminary results suggest that other approaches such as convalescent plasma therapy and lung radiation therapy may have some efficacy. The current clinical evidence for potential treatments is preliminary-often small retrospective series or early results of randomized trials-and the science is evolving rapidly. The long-term results from large, well-designed randomized controlled trials will provide definitive evidence for therapeutic effectiveness and are likely months away. The trial landscape for promising therapies is described.

Pharmacological treatment of COVID-19: an opinion paper.

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.

Role of Antiviral Drugs in Management of Mild and Moderate Coronavirus Disease-19: A Systematic Review

This study was conducted to determine the objective role of antiviral drugs such as arbidol, lopinavir/ritonavir, and others in improving clinical symptoms, decreasing duration of hospitalization, and decreasing duration of viral shedding in patients with mild and moderate COVID-19 infection. A systematic literature search was carried out on Google Scholar and PubMed databases, using the keywords "COVID-19”, "Antiviral”, "Treatment”, and "Symptomatic” in various combinations. Observational studies, cohort and case control studies, and clinical trials published in English with full-text available were included in the study. Data extraction was carried out from selected studies, and all statistical analysis for the study was carried out using Microsoft Excel. The key outcomes studied were time to negative PCR, duration of clinical stay, time to clinical improvement, and occurrence of adverse events. Seven studies were selected for final review after rigorous selection process. Data of total 4734 participants was analyzed, the majority of which were females (n=2810, 59.3%). The majority of participants had mild disease (n=4197, 88.65%). Average time for negative RT-PCR in the included treatment groups was 13.5 days, whereas the average duration of hospitalization was 14.9 days for the treatment groups. Adverse reactions such as ECG changes, gastrointestinal symptoms, secondary bacterial infections, and hepatic and renal dysfunction were scarcely reported in the included studies. There is no clear benefit in terms of duration of hospitalization and time to negative PCR with the use of various antiviral regimens in mild disease;however, these drugs did play a role in limiting disease progression in the participant population. Pending further evidence, the use of these drugs for the management of COVID-19 is not recommend in patients with mild disease. © 2022, The Running Line. All rights reserved.

A Practical Approach in Refining Binary Outcome for Treatment Effect of COVID-19 According to Geographical Diversity.

The recent COVID-19 pandemic has drawn attention to health and economics worldwide. Initially, diseases only ravage local populations, while a pandemic could aggravate global economic burdens. Lopinavir/Ritonavir is an anti-HIV drug that was used on small scale patients during SARS, but its effectiveness for COVID-19 treatment is still unclear. Previous studies or meta-analysis have retrieved clinical data of subgroup analysis to evaluate the efficacy and safety of Lopinavir/Ritonavir for the treatment of COVID-19 in a few affected regions. However, geographical diversity and small number of studies bias correction were not achieved in such subgroup analysis of published meta-analysis. The present study demonstrates a practical approach in refining the binary outcome for COVID-19 treatment of Lopinavir/Ritonavir according to geographical location diversity and small number of studies (less than or equal to five) for subgroup analysis. After performing practical approach, the risk of adverse event with LPV/RTV for treatment of COVID-19 becomes nonsignificant compared to previous meta-analysis. Furthermore, we also notice heterogeneity of random effect of meta-analysis may be declined after proposed adjustment. In conclusion, proposed practical approach is recommend for performing a subgroup analysis to avoid concentration in a single geographical location and small number of studies bias.

Efficacy of lopinavir/ritonavir plus interferon beta compared to hydroxychloroquine in the treatment of COVID-19: A retrospective observational study

Introduction: Although a long time past since COVID-19 was broken out, it is hard to determine which pharmacological combination regimen is more efficacious. The present study aimed to evaluate the efficacy of lopinavir/ritonavir (LPV/r) plus interferon (IFN) beta-1a regimen compared to the hydroxychloroquine (HCQ) regimen in moderately ill patients with COVID-19. Methods: A multiple-centre retrospective observational case-controlled study was performed between March and September 2020, including adults with confirmed COVID-19. The patients were categorised into age- and sex-matched two groups;LPV/r plus IFN beta-1a (n = 102) and HCQ (n = 298) regimens. Clinical outcomes and mortality rates were compared between the groups. Results: LPV/r plus interferon (INF) beta-1a regimen had improved none of the clinical outcomes and mortality rate compared to the HCQ regimen. The length of stay (LOS) in the hospital and the need for oxygen therapy were slightly worse in the LPV/r plus INF beta-1a regimen (4.73 ± 2.93 days, 63%) than in the HCQ group (3.74 ± 3.30 days, 48.3%). No statistically significant difference was observed between the two groups in care of intensive care unit (ICU) admission, LOS in ICU, the need for non-invasive ventilation and the need for invasive mechanical ventilation as well as in-hospital mortality rate. Conclusions: LPV/r plus IFN beta-1a regimen did not show any meaningful improvement in clinical outcomes or mortality compared to the HCQ regimen. Larger randomised controlled trials are needed to assess the efficacy of this combination further. [ FROM AUTHOR]

Drug-drug interactions of ritonavir-boosted SARS-CoV-2 protease inhibitors in solid organ transplant recipients: experience from the initial use of lopinavir-ritonavir.

OBJECTIVES: To review the drug-drug interactions between tacrolimus and lopinavir/ritonavir in 23 patients who received solid organ transplant during the first wave of COVID-19 and to determine the efficacy as well as safety of prednisone monotherapy. METHODS: Observational study performed between March and June 2020 in solid organ transplant recipients admitted with an established diagnosis of SARS-CoV-2 infection who received lopinavir/ritonavir (≥2 doses). Once lopinavir/ritonavir therapy was initiated, calcineurin inhibitor treatment was temporarily switched to prednisone monotherapy (15-20 mg/d) to avoid drug-drug interactions and toxicity. After lopinavir/ritonavir treatment completion, immunosuppressive treatment was restarted with reduced doses of prednisone-tacrolimus (target minimum blood concentration -C0- approximately 5 ng/mL). Patients were observed for 3 months to confirm the absence of rejection. RESULTS: The median time from discontinuation of tacrolimus to initiation of lopinavir/ritonavir was 14 hours (interquartile range [IQR], 12-15) and from discontinuation of lopinavir/ritonavir to resumption of tacrolimus 58 hours (IQR, 47-81). The duration of lopinavir/ritonavir treatment was 7 days (IQR, 5-7). Nine of the 21 (42.8%) patients on tacrolimus treatment had C0 above the cutoff point after lopinavir/ritonavir initiation, despite having been substituted with prednisone before lopinavir/ritonavir initiation. Three patients had very high concentrations (>40 ng/mL) and developed toxicity. No episodes of acute rejection were diagnosed. DISCUSSION: We did not observe toxicity in patients for whom tacrolimus was discontinued 24 hours before starting lopinavir/ritonavir and reintroduced at half dose 48 to 72 hours after lopinavir/ritonavir discontinuation. Prednisone monotherapy during lopinavir/ritonavir therapy was safe with no episodes of acute rejection. Experience with lopinavir/ritonavir may be applicable to the use of nirmatrelvir/ritonavir, but larger multicentre studies are needed to confirm these findings.

Camostat Mesylate Versus Lopinavir/Ritonavir in Hospitalized Patients With COVID-19-Results From a Randomized, Controlled, Open Label, Platform Trial (ACOVACT).

Background: To date, no oral antiviral drug has proven to be beneficial in hospitalized patients with COVID-19. Methods: In this randomized, controlled, open-label, platform trial, we randomly assigned patients ≥18 years hospitalized with COVID-19 pneumonia to receive either camostat mesylate (CM) (considered standard-of-care) or lopinavir/ritonavir (LPV/RTV). The primary endpoint was time to sustained clinical improvement (≥48 h) of at least one point on the 7-category WHO scale. Secondary endpoints included length of stay (LOS), need for mechanical ventilation (MV) or death, and 29-day mortality. Results: 201 patients were included in the study (101 CM and 100 LPV/RTV) between 20 April 2020 and 14 May 2021. Mean age was 58.7 years, and 67% were male. The median time from symptom onset to randomization was 7 days (IQR 5-9). Patients in the CM group had a significantly shorter time to sustained clinical improvement (HR = 0.67, 95%-CI 0.49-0.90; 9 vs. 11 days, p = 0.008) and demonstrated less progression to MV or death [6/101 (5.9%) vs. 15/100 (15%), p = 0.036] and a shorter LOS (12 vs. 14 days, p = 0.023). A statistically nonsignificant trend toward a lower 29-day mortality in the CM group than the LPV/RTV group [2/101 (2%) vs. 7/100 (7%), p = 0.089] was observed. Conclusion: In patients hospitalized for COVID-19, the use of CM was associated with shorter time to clinical improvement, reduced need for MV or death, and shorter LOS than the use of LPV/RTV. Furthermore, research is needed to confirm the efficacy of CM in larger placebo-controlled trials. Systematic Review Registration: [https://clinicaltrials.gov/ct2/show/NCT04351724, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001302-30/AT], identifier [NCT04351724, EUDRACT-NR: 2020-001302-30].

Optimal Drug Regimen and Combined Drug Therapy and Its Efficacy in the Treatment of COVID-19: A Within-Host Modeling Study.

The COVID-19 pandemic has resulted in more than 524 million cases and 6 million deaths worldwide. Various drug interventions targeting multiple stages of COVID-19 pathogenesis can significantly reduce infection-related mortality. The current within-host mathematical modeling study addresses the optimal drug regimen and efficacy of combination therapies in the treatment of COVID-19. The drugs/interventions considered include Arbidol, Remdesivir, Interferon (INF) and Lopinavir/Ritonavir. It is concluded that these drugs, when administered singly or in combination, reduce the number of infected cells and viral load. Four scenarios dealing with the administration of a single drug, two drugs, three drugs and all four are discussed. In all these scenarios, the optimal drug regimen is proposed based on two methods. In the first method, these medical interventions are modeled as control interventions and a corresponding objective function and optimal control problem are formulated. In this framework, the optimal drug regimen is derived. Later, using the comparative effectiveness method, the optimal drug regimen is derived based on the basic reproduction number and viral load. The average number of infected cells and viral load decreased the most when all four drugs were used together. On the other hand, the average number of susceptible cells decreased the most when Arbidol was administered alone. The basic reproduction number and viral load decreased the most when all four interventions were used together, confirming the previously obtained finding of the optimal control problem. The results of this study can help physicians make decisions about the treatment of the life-threatening COVID-19 infection.

CHALLENGES REGARDING THE INTERACTION BETWEEN PSYCHOTROPICS AND COVID-19 CO-MEDICATION

Coronavirus disease 19 (COVID-19) pandemic is at the moment the main topic of interest regarding medical science and research. Responsible for the disease is a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) accountable for over 118 million cases and a total of 2.61 million deaths worldwide (July 2020). Drug treatment for infected COVID-19 patients represents a difficult task, since there is no currently licensed specific antiviral for SARS-CoVs, the clinical approach of these patients remains the symptomatic one and also providing supportive care if needed. The clinical approach becomes more of a challenge especially if one has a co-existing psychiatric illness under psychotropic treatment. This concern is raised due to potential drug-to-drug interactions (DDIs) between antiviral agents and psychotropics, not only by common metabolic pathways regarding P450 cytocromial enzymes but also by pharmacological synergism regarding common adverse effects. Thus, we searched to identify studies published in PubMed medical database to support clinical practice in these situations and found that mostly all main psychotropics are implied in DDIs with the antivirals used to treat COVID-19 infection. Therefore, the clinical approach in treating COVID-19 patients with antiviral agents remains a challenge especially for those who have a comorbid psychiatric illness and are under treatment with psychotropics.

Safety of Drugs Used during the First Wave of COVID-19: A Hospital-Registry-Based Study.

The emergency of the coronavirus disease 2019 (COVID-19) pandemic led to the off-label use of drugs without data on their toxicity profiles in patients with COVID-19, or on their concomitant use. Patients included in the COVID-19 Patient Registry of a tertiary hospital during the first wave were analyzed to evaluate the adverse drug reactions (ADRs) with the selected treatments. Twenty-one percent of patients (197 out of 933) had at least one ADR, with a total of 240 ADRs. Patients with ADRs were more commonly treated with multiple drugs for COVID-19 infection than patients without ADRs (p < 0.001). They were younger (median 62 years vs. 70.1 years; p < 0.001) and took less medication regularly (69.5% vs. 75.7%; p = 0.031). The most frequent ADRs were gastrointestinal (67.1%), hepatobiliary (10.8%), and cardiac disorders (3.3%). Drugs more frequently involved included lopinavir/ritonavir (82.2%), hydroxychloroquine (72.1%), and azithromycin (66.5%). Although most ADRs recovered without sequelae, fatal cases were described, even though the role of the disease could not be completely ruled out. In similar situations, efforts should be made to use the drugs in the context of clinical trials, and to limit off-label use to those drugs with a better benefit/risk profile in specific situations and for patients at high risk of poor disease prognosis.

Nitric-oxide enriched plasma-activated water inactivates 229E coronavirus and alters antiviral response genes in human lung host cells

The ongoing pandemic caused by the novel comnavirus, SARS-CoV-2, is influencing global health. Moreover, there is a major threat of future coronaviruses affecting the entire world in a similar, or even more dreadful, manner. Therefore, effective and biocompatible therapeutic options against comnaviruses are urgently needed. To address this challenge, medical specialists require a well-informed and safe approach to treating human coronaviruses (HCoVs). Herein, an environmental friendly approach for viral inactivation, based on plasma technology, was considered. A microwave plasma system was employed for the generation of the high amount of gaseous nitric oxide to prepare nitric oxide enriched plasma-activated water (NO-PAW), the effects of which on coronaviruses, have not been reported to date. To determine these effects, alpha-HCoV-229E was used in an experimental model. We found that NO-PAW treatment effectively inhibited comnavirus infection in host lung cells, visualized by evaluating the cytopathic effect and expression level of spike proteins. Interestingly, NO-PAW showed minimal toxicity towards lung host cells, suggesting its potential for therapeutic application. Moreover, this new approach resulted in viral inactivation and greatly improved the gene levels involved in host antiviral responses. Together, our findings provide evidence of an initiation point for further progress toward the clinical development of antiviral treatments, including such comnaviruses.

Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study.

OBJECTIVE: The objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators. DESIGN: Prospective descriptive multicenter cohort study. SETTING: 26 Intensive care units (ICU) from Andalusian region in Spain. PATIENTS OR PARTICIPANTS: Consecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30. INTERVENTIONS: None. VARIABLES: Variables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied. RESULTS: 495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%; 14 days mortality: 81/422 (19.2%); 28 days mortality: 121/422 (28.7%); 6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72h post-ICU admission <6.5%, and thrombocytopenia whereas the use of lopinavir/ritonavir was a protective factor. CONCLUSION: Age, APACHE II, SOFA>value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks. Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab. Lopinavir/ritonavir administration is identified as a protective factor.

A Brief Outline of COVID 19 Specific Therapy in Hospitalised Patients In India

COVID 19 pandemic has a significant impact on global public health and economies. Scientists and researchers all over the world are endeavouring in search of specific drug against COVID19 virus. For a novel emerging virus, specific antiviral drug takes time before its approval for clinical use as RCTs are expensive and time consuming. In Indian perspective, many drugs which are currently under clinical trial are unavailable. Reviewing available published and unpublished papers, we intend to throw light on the drugs that can be used in the interim in India till further evidence come. Pending sufficient evidence remdesivir, favipirvair,tocilizumab,lopinavir-ritonavir with or without ribavirin;hydroxychloroquine or convalescent plasma can be considered. © 2020 Indian Medical Association. All rights reserved.

Influence of traditional Chinese medicines on the in vivo metabolism of lopinavir/ritonavir based on UHPLC-MS/MS analysis.

A fast, reliable, and cost-effective liquid chromatography-tandem mass spectrometry method was established to determine the effects of the traditional Chinese medicine employed to treat coronavirus disease 2019, namely, Lianhua Qingwen granules, Huoxiang Zhengqi capsules, Jinhua Qinggan granules, Shufeng Jiedu capsules, and Angong Niuhuang pills, on the pharmacokinetics of lopinavir/ritonavir in rats. Blood samples were prepared using the protein precipitation method and atazanavir was selected as the internal standard (IS). Separation was performed on an Agilent ZORBAX eclipse plus C18 (2.1 mm × 50 mm, 1.8 µm) column using acetonitrile and water containing 0.1% formic acid as the mobile phase for gradient elution. The flow rate was 0.4 mL/min and the injection volume was 2 µL. Agilent Jet Stream electrospray ionization was used for mass spectrometry detection under positive ion multiple reaction monitoring mode at a transition of m/z 629.3→447.3 for lopinavir, m/z 721.3→296.1 for ritonavir, and m/z 705.4→168.1 for the IS. The method showed good linearity in the concentration range of 25-2500 ng/mL (r=0.9981) for lopinavir and 5-500 ng/mL (r=0.9984) for ritonavir. The intra-day and inter-day precision and accuracy were both within ±15%. Items, such as dilution reliability and residual effect, were also within the acceptable limits. The method was used to determine the effects of five types of traditional Chinese medicines on the pharmacokinetics of lopinavir/ritonavir in rats. The pharmacokinetic results showed that the half-life of ritonavir in the groups administered Lianhua Qingwen granules and Huoxiang Zhengqi capsules combined with lopinavir/ritonavir was prolonged by approximately 1.5- to 2-fold relative to that in the control group. Similarly, the pharmacokinetic parameters of lopinavir were altered. Overall, the results of this study offer important theoretical parameters for the effective clinical use of five types of traditional Chinese medicines combined with lopinavir/ritonavir to reduce the occurrence of clinical adverse reactions.

COVID-19 Global Pandemic Fight by Drugs: A Mini-Review on Hope and Hype

Coronavirus disease 2019 (Covid-19), a serious disease caused by the Severe Acute Res-piratory Syndrome-Corona Virus-2 (SARS-CoV-2), was firstly identified in the city of Wuhan of China in December 2019, which then spread and became a global issue due to its high transmission rate. To date, the outbreak of COVID-19 has resulted in infection to 230,868,745 people and the death of 4,732,669 patients. It has paralyzed the economy of all the countries worldwide. Considering the possible mutations of SARS-CoV-2, the current medical emergency requires a longer time for drug design and vaccine development. Drug repurposing is a promising option for potent therapeutics against the pandemic. The present review encompasses various drugs or appropriate combinations of already FDA-approved antimalarial, antiviral, anticancer, anti-inflammatory, and antibiotic therapeu-tic candidates for use in the clinical trials as a ray of hope against COVID-19. It is expected to deliver better clinical and laboratory outcomes of drugs as a prevention strategy for the eradication of the dis-ease.

Meta-analysis of arbidol versus lopinavir/ritonavir in the treatment of coronavirus disease 2019.

OBJECTIVES: To systematically evaluate the efficacy and safety of arbidol and lopinavir/ritonavir (LPV/r) in the treatment of coronavirus disease 2019 (COVID-19) using a meta-analysis method. METHODS: The China Knowledge Network, VIP database, WanFang database PubMed database, Embase database, and Cochrane Library were searched for a collection of comparative studies on arbidol and lopinavir/ritonavir in the treatment of COVID-19. Meta-analysis was used to evaluate the efficacy and safety of Arbidol and lopinavir/ritonavir in the treatment of COVID-19. RESULTS: The results of the systematic review indicated that Arbidol had a higher positive-to-negative conversion rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid on Day 7 (p = 0.03), a higher positive-to-negative conversion rate of SARS-CoV-2 nucleic acid on Day 14 (p = 0.006), a higher improvement rate of chest computed tomography on Day 14 (p = 0.02), a lower incidence of adverse reactions (p = 0.002) and lower rate of mortality (p = 0.007). There was no difference in the rate of cough disappearance on Day 14 (p = 0.24) or the rate of severe/critical illness (p = 0.07) between the two groups. CONCLUSIONS: Arbidol may be superior to lopinavir/ritonavir in the treatment of COVID-19. However, due to the small number of included studies and the number of patients, high-quality multicenter large-sample randomized double-blind controlled trials are still needed for verification.