Dissecting the Drug Development Strategies Against SARS-CoV-2 Through Diverse Computational Modeling Techniques

Abstract

The world of the twenty-first century has not experienced such a lockdown situation before, which leads to a complete shutdown of economy not until the novel coronavirus disease 2019 (COVID-19) came caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It becomes an unacceptable global threat to human lives. The COVID-19 has been known only worldwide in the last few months, but it is spreading in a speed of light from Wuhan, China, to the rest of the world. About 2 crore of people have been infected and more than 7 lakh of people have died worldwide till now due to the deadly SARS-CoV-2 infection. There are still no drugs exclusively available in the market for the treatment of SARS-CoV-2 infection, though supportive treatment of hydroxychloroquine, ribavirin, favipiravir, and remdesivir have shown clinical evidences to treat COVID-19. Therefore, it is utmost importance for the medicinal chemists to design and discover novel drugs urgently to rescue or to protect the humanity worldwide from this deadly virus. However, lack of experimental evidences and understanding the behavior of the SARS-CoV-2 within this short period may hinder the process of drug discovery. Still a ray of hope resides in the structural features of SARS-CoV-2 and related coronaviruses (SARS-CoV and MERS-CoV) as these are homologous. Therefore, depending on the established viral target proteins (spike protein, ACE-2, 3CL pro , PL pro , RdRp, helicase, as well as other viral proteins), novel chemical entities may be designed. In this context, several computational modeling approaches (generally structure-based modeling techniques) may be utilized which are cost-effective and less time-consuming. Different structure-based modeling techniques, namely, homology modeling, robust molecular docking, molecular dynamics simulation, and structure-based pharmacophore mapping followed by in silico virtual screening, may be effective and fruitful approaches to design compounds against SARS-CoV-2. In this chapter, various structure-based drug design and discovery strategies from target identification that could be optimized against SARS-CoV-2 have been discussed in detail. Additionally, ongoing and previously reported computational modeling techniques performed by different groups of researchers on various SARS-CoV-2 target proteins have been highlighted elaborately. In addition to the identification techniques of drugs, this chapter also discloses their binding mode of action along with the pharmacokinetics and toxicity criteria computed by modeling techniques. This chapter, therefore, may be a stepping-stone for the researchers to open up a new horizon in the discovery of novel anti-coronavirus drugs in the future.

Ligand-based quantitative structural assessments of SARS-CoV-2 3CLpro inhibitors: An analysis in light of structure-based multi-molecular modeling evidences

“…Certainly, the disease spread at lightning speed to the rest of the world, and therefore, the World Health Organization (WHO) announced this infection as coronavirus disease 2019 (COVID-19) [2] . This disease has been produced by the infection of the novel coronavirus or severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) [3] , [4] . Consequently, this novel coronavirus is found to be closely related to a similar virus, i.e., SARS-CoV spread during 2003 [1] .…”

“…Several anti-coronaviral viral proteins have already been established as promising targets for COVID-19 drug discovery. These include helicase, RNA-dependent RNA polymerase (RdRp), hemagglutinin esterase along with the structural and other non-structural proteins which can be targeted for anti-SARS-CoV-2 drug discovery [ 3 , 16 ].…”

“…Our group has already performed several extensive studies on the previous SARS-CoV inhibitors [ 3 , [18] , [19] , [24] , [25] , [26] , [27] , [28] , [29] , [30] ]. In this study, we have reported the structural analysis of 69 diverse SARS-CoV-2 3CL pro inhibitors by the regression-based quantitative structure-activity relationship (QSAR) methodologies to identify the fundamental structural features having crucial effects on SARS-CoV-2 3CL pro inhibition.…”

Potential bioactive compounds of medicinal plants against new Coronavirus (SARS-CoV-2): A review

“…The potential activity of curcumin against SARS-CoV-2 has been demonstrated by (14), using the molecular docking method to determine the affinity of binding between the active molecule and COVID-19 proteases[A12] 15,16 . 6LU7 AND 6Y2E expressed in kcal/mol obtain favorable results and recommend the plant species for future studies[A13] [17][18][19] . Due to its various properties, curcumin has the potential for the development of new drugs 4 .…”

“…SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID- 19), is a new type of Coronavirus that currently has claimed 5,682,389 of infected people and 354,944 deaths globally. In Ecuador, the facts are also alarming, with 38,103 confirmed cases and 3,275 deaths 1 .…”