Comprehensive review on the prevailing COVID-19 therapeutics and the potential of repurposing SARS-CoV-1 candidate drugs to target SARS-CoV-2 as a fast-track treatment and prevention option

Abstract

The recent seemingly uncontrollable pandemic caused by the novel severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has been able to spread quickly due to the non-availability of effective antivirals or vaccines. The virus has structural and non-structural proteins that are considered as possible targets. Receptor recognition is the critical determinant and preliminary phase of viral infection to enter the host cell and causes tissue tropism. We have conducted a comprehensive review of relevant publication on in vitro, in silico, in vivo and clinical evaluation of drug candidates ranging from broad-spectrum antivirals to natural molecules targeted towards viral spike protein in addition to evaluate their suitability as therapies based on an analysis of the similarities between SARS-CoV-1 and SARS-CoV-2. In general, antiviral targets are based on two strategies, either targeting the host or the host's immune cell. We have reviewed the available details on the SARS-CoV-2 strain's host-viral binding sites entry mechanism, alongside recently tested effective antivirals. The hypothesis of this review may provide clear insight for researchers and physicians who are struggling to narrow down scientific options to control the current pandemic. Overall, we found that the promising efficacious drug candidates reported against SARS-CoV-1 could be considered for drug repurposing; this might help to identify a potential drug for therapeutic measures and development of vaccine for COVID-19.

Keywords: COVID-19; SARS-CoV-1; Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2); antivirals; repurposing.

Figure 1

Schematic representation of similarities between SARS-CoV-2 and SARS-CoV-1 and overview of possible targets for SARS-CoV-2 antiviral prediction. (A) The entry process for both (SARS-CoV-1 and SARS-CoV-2) access the similar mechanism where ACEII is the common receptor and prime with TMPSSR2 and enters into the host cell. Once it enters with the help of spike protein, both cells undergo Clathrin mediated endocytosis with the association of AP2 associated protein kinase. Therefore, the effective antivirals studied for SARS-CoV-1 could be used for SARS-COV-2 for better prediction as it has same mechanism. (B) Domain structure of SARS-CoV-1 and SARS-CoV-2 where S1 and S2 protein. SARS-CoV-2, severe acute respiratory syndrome-related coronavirus 2; RBD, receptor binding domain; RBM, receptor binding motif; HR, heptad repeats; NTD, N terminal domain; CTD, C terminal domain; CD, cytoplasmic domain; TM, transmembrane; CT, cytoplasmic tail.