Exploring existing drugs: proposing potential compounds in the treatment of COVID-19

Abstract

The COVID-19 situation had escalated into an unprecedented global crisis in just a few weeks. On the 30 th of January 2020, World Health Organization officially declared the COVID-19 epidemic as a public health emergency of international concern. The confirmed cases were reported to exceed 105,856,046 globally, with the death toll of above 2,311,048, according to the dashboard from Johns Hopkins University on the 7 th of February, 2021, though the actual figures may be much higher. Conserved regions of the South Asian strains were used to construct a phylogenetic tree to find evolutionary relationships among the novel virus. Off target similarities were searched with other microorganisms that have been previously reported using Basic Local Alignment Search Tool (BLAST). The conserved regions did not match with any previously reported microorganisms or viruses, which confirmed the novelty of SARS-CoV-2. Currently there is no approved drug for the prevention and treatment of COVID-19, but researchers globally are attempting to come up with one or more soon. Therapeutic strategies need to be addressed urgently to combat COVID-19. Successful drug repurposing is a tool that uses old and safe drugs, is time effective and requires lower development costs, and was thus considered for the study. Molecular docking was used for repurposing drugs from our own comprehensive database of approximately 300 highly characterized, existing drugs with known safety profile, to identify compounds that will inhibit the chosen molecular targets -SARS-CoV-2, ACE2, and TMPRSS2. The study has identified and proposed twenty seven candidates for further in vitro and in vivo studies for the treatment of SARS-CoV-2 infection.

Nanotechnology and COVID-19: quo vadis?

“…This is one of the most significant impasses to significantly reduce the number of deaths from this virus (Kostarelos 2020 ). The simplest and quickest way to establish a drug for the treatment of COVID-19 is from drug repurposing, which consists of giving new uses to drugs already approved for other diseases (Kabir et al 2021 ).…”

Exploring the disruption of SARS-CoV-2 RBD binding to hACE2

“…The RBD of the spike protein is an often-used target in order to inhibit its interaction with hACE2 receptors, thereby preventing viral infection. Many studies have identified potential inhibitors using molecular docking and/or molecular dynamics (MD) simulations against solely the RBD (Faheem et al, 2020;Prajapat et al, 2020;Trezza et al, 2020;Kumar et al, 2021;Hu et al, 2022;Wu et al, 2022) or solely the hACE2 receptor (Benítez-Cardoza and Vique-Sánchez, 2020; Kabir et al, 2021). Very few studies have analyzed the interaction of small drug-like molecules with the RBD-hACE2 interface.…”

Effectivity of repurposed drugs against SARS-CoV-2 infections, A hope for COVID 19: inhibitor modelling studies by docking and molecular dynamics

“…So the whole procedure becomes time-consuming and expensive with a high possibility of failure. So as an alternative, another novel approach to identify new therapeutic option is drug repurposing 10 , 11 . Drug repositioning is the main activity of drug repurposing which involves the investigation of new therapeutic indications of existing drugs.…”