Therapeutics for COVID-19: from computation to practices—where we are, where we are heading to

Abstract

After the 1918 Spanish Flu pandemic caused by the H1N1 virus, the recent coronavirus disease 2019 (COVID-19) brought us to the time of serious global health catastrophe. Although no proven therapies are identified yet which can offer a definitive treatment of the COVID-19, a series of antiviral, antibacterial, antiparasitic, immunosuppressant drugs have shown clinical benefits based on repurposing theory. However, these studies are made on small number of patients, and, in majority of the cases, have been carried out as nonrandomized trials. As society is running against the time to combat the COVID-19, we present here a comprehensive review dealing with up-to-date information of therapeutics or drug regimens being utilized by physicians to treat COVID-19 patients along with in-depth discussion of mechanism of action of these drugs and their targets. Ongoing vaccine trials, monoclonal antibodies therapy and convalescent plasma treatment are also discussed. Keeping in mind that computational approaches can offer a significant insight to repurposing based drug discovery, an exhaustive discussion of computational modeling studies is performed which can assist target-specific drug discovery.

Peptide and peptide-based inhibitors of SARS-CoV-2 entry

“…As it is the case of many disorders, infectious or not, in-silico strategies for the design and screening of active compounds, as well as for studying the dynamics of the involved proteins are key to global efforts aiming to identify novel therapeutics and vaccines [ [151] , [152] , [153] ], also in the context of the SARS-CoV-2 pandemic [ 53 , [154] , [155] , [156] , [157] , [158] , [159] , [160] , [161] , [162] ]. In this section, we provide an overview of computational approaches used for delivering timely predictions of peptide and peptide-based inhibitors targeting the virus's entry mechanism.…”

Identification of Small Molecule Inhibitors of the Deubiquitinating Activity of the SARS-CoV-2 Papain-Like Protease: in silico Molecular Docking Studies and in vitro Enzymatic Activity Assay

“…In a recent paper by Alamri et al a structured-based computational approach was utilized to identify compounds that may act as pan-PL pro inhibitors and could be developed further as antiviral agents (Alamri et al, in press ). Given the current situation, in silico methods have made it possible for large libraries of existing approved compounds to be screened in a relatively fast manner (Ojha et al, 2020 ). The structures of the hits identified from these computational studies could be optimized as part of the drug discovery process (Ojha et al, 2020 ).…”

“…Given the current situation, in silico methods have made it possible for large libraries of existing approved compounds to be screened in a relatively fast manner (Ojha et al, 2020 ). The structures of the hits identified from these computational studies could be optimized as part of the drug discovery process (Ojha et al, 2020 ). In addition to synthetic pharmacological compounds, herbal constituents can be screened in the same manner and this method has been described in many papers (Bhowmik et al, 2020 ; Chikhale et al, 2020 ; Ghosh et al, 2020 ; Gupta et al, 2020 ; Jena et al, 2020 ; Krupanidhi et al, 2020 ; Muhseen et al, 2020 ; Sinha et al, 2020 ; Subbaiyan et al, 2020 ).…”

Systematic Search for SARS-CoV-2 Main Protease Inhibitors for Drug Repurposing: Ethacrynic Acid as a Potential Drug

“…This large body of knowledge, accumulated in a short time thanks to the enormous collective effort of the scientific community, on the structure and function of has stimulated a number of works and methodology for in silico drug design [ 12 , 13 , 14 , 15 , 16 ]. Recently drug repositioning has been recognized as an alternative approach that explores new indications for approved (or also abandoned) drugs.…”