The Drug Repurposing for COVID-19 Clinical Trials Provide Very Effective Therapeutic Combinations: Lessons Learned From Major Clinical Studies

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.

A Detailed Overview of Immune Escape, Antibody Escape, Partial Vaccine Escape of SARS-CoV-2 and Their Emerging Variants With Escape Mutations

“…Some large clinical trials with most patients are ACTT-1, ACTT-2, and RECOVERY trials. These trials results showed the best therapeutic option, such as remdesivir or its combination with different antibodies (259). All the chemical components based therapeutic molecules have been developed using the drug targets, especially the primary drug target proteins of the virus or the host (262).…”

“…Several small molecule-based therapeutics have been approved for the treatment of COVID-19. In these cases, therapeutic development strategies have mainly been used to repurpose drugs (247,(259)(260)(261). Several clinical trials have been performed from small-size to large-size depending on the number of COVID-19 patients to understand the effectiveness of repurposing drugs.…”

The Safety and Immunogenicity of the BNT162b2 mRNA COVID-19 Vaccine in Japanese Patients after Allogeneic Stem Cell Transplantation

“…HSCT patients are known to be highly immunocompromised due to past chemotherapy or immunosuppressive agents for graft-versus-host disease (GVHD). Prevention of COVID-19 is therefore critically important in these patients, while some treatments, including immunotherapy, are considered to be promising strategies against COVID-19 [2,3].…”

A Comprehensive Review of Drug Repurposing Strategies against Known Drug Targets of COVID-19

“…This creates a lag in the productivity of pharmaceutical research to develop a new drug, resulting in a persistent gap between therapeutic needs and available treatments. Despite base evidence being of variable quality, existing drugs have been repurposed in the war against the coronavirus pandemic [11]. Even though vaccines have been made available for the general populace, there is no specific treatment for the patients suffering from the disease.…”