Abstract
SARS-CoV-2 has spread across the globe in no time. In the beginning, people suffered due to the absence of efficacious drugs required to treat severely ill patients. Nevertheless, still, there are no established therapeutic molecules against the SARS-CoV-2. Therefore, repurposing of the drugs started against SARS-CoV-2, due to which several drugs were approved for the treatment of COVID-19 patients. This paper reviewed the treatment regime for COVID-19 through drug repurposing from December 8, 2019 (the day when WHO recognized COVID-19 as a pandemic) until today. We have reviewed all the clinical trials from RECOVERY trials, ACTT-1 and ACTT-2 study group, and other major clinical trial platforms published in highly reputed journals such as NEJM, Lancet, etc. In addition to single-molecule therapy, several combination therapies were also evaluated to understand the treatment of COVID-19 from these significant clinical trials. To date, several lessons have been learned on the therapeutic outcomes for COVID-19. The paper also outlines the experiences gained during the repurposing of therapeutic molecules (hydroxychloroquine, ritonavir/ lopinavir, favipiravir, remdesivir, ivermectin, dexamethasone, camostatmesylate, and heparin), immunotherapeutic molecules (tocilizumab, mavrilimumab, baricitinib, and interferons), combination therapy, and convalescent plasma therapy to treat COVID-19 patients. We summarized that anti-viral therapeutic (remdesivir) and immunotherapeutic (tocilizumab, dexamethasone, and baricitinib) therapy showed some beneficial outcomes. Until March 2021, 4952 clinical trials have been registered in ClinicalTrials.gov toward the drug and vaccine development for COVID-19. More than 100 countries have participated in contributing to these clinical trials. Other than the registered clinical trials (medium to large-size), several small-size clinical trials have also been conducted from time to time to evaluate the treatment of COVID-19. Four molecules showed beneficial therapeutic to treat COVID-19 patients. The short-term repurposing of the existing drug may provide a successful outcome for COVID-19 patients. Therefore, more clinical trials can be initiated using potential anti-viral molecules by evaluating in different phases of clinical trials.
Highlights
The COVID-19 pandemic has created a global health crisis and massive mortality of over two million people worldwide
The use of this therapeutic corticosteroid resulted in lower 28-day mortality among the hospitalized with COVID-19 patients who were receiving either oxygen alone or invasive mechanical ventilation support (RECOVERY clinical trial platform)
We have tried to evaluate the available data on repurposing drugs from the beginning of their trials, including the lessons learned from the experience from using various therapeutic molecules to treat the COVID-19 patients like hydroxychloroquine, ritonavir/lopinavir, favipiravir, remdesivir, ivermectin, dexamethasone, camostatmesylate, tocilizumab, mavrilimumab, baricitinib, and interferons (IFN)
Summary
The COVID-19 pandemic has created a global health crisis and massive mortality of over two million people worldwide. Physicians and clinicians had initially described the conditions as “pneumonia of unknown etiology.”. The clinical symptoms associated with this disease include a broad-spectrum range of mild to severe respiratory problems. The fatality rate is estimated to be 2–5%. The fatality rate varies from country to country (Khafaie and Rahim, 2020). It was observed that the mortality rate was high among elderly patients and patients with comorbidities such as diabetes, cardiovascular diseases, immune-suppressive diseases, and cancer (Kang and Jung, 2020; Rahim et al, 2020; Barbui et al, 2021). All physicians and clinicians have tried to find effective therapeutic molecules to treat this viral disease using repurposed drugs.
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