In Silico Pharmacology (2021) 9:45 https://doi.org/10.1007/s40203-021-00105-x

ORIGINAL RESEARCH

In silico studies of Potency and safety assessment of selected trial drugs for the treatment of COVID‑19

Peter Ifeoluwa Adegbola1 · Olumide Samuel Fadahunsi1 · Aanuoluwa Eunice Adegbola2 · Banjo Semire2

Received: 14 May 2021 / Accepted: 12 July 2021 © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021

Abstract SARS-CoV-2 has caused millions of and hundreds of thousands of deaths globally. Presently, no cure for SARS- CoV-2 is available; thus, all hands are on deck for new drug discovery. Although, several studies have reported the potentials of some already approved drugs for the treatment of COVID-19. This study attempted to compare the potency and safety of some these trial drugs via in silico methods. The binding afnity and interactions of the trial drugs with proteins involved in viral polyprotein processing (Papain like protease (PLpro) and Chymotrypsin like-protease (3-CLpro), viral replication (RNA dependent RNA polymerase (RdRp)) and host protease were studied in this work. The pharmacokinetic properties and toxicity potentials of the trial drugs were also predicted using vNN Web Server for ADMET Predictions. From the results, Merimepodib and Dexamethaxone demonstrated the most signifcant inhibitory potential against the PLpro. The binding afnity (∆G°) for merimepodib was − 7.2 kcal/mol while the inhibition constant was 6.3 µM. The binding afnity of the inhibitors for CLpro ranged from − 5.6 to − 9.5 kcal/mol. whereas Lopinavir (− 7.7 kcal/mol) exhibited the strongest afnity for RdRp. Overall, our results showed that all the ligands have a higher afnity for the 3-Chymotrypsin like protease than the other proteins (PLpro, RdRp, and Host protease). Among these compounds lopinavir, merimepodib and dexametha- sone could be inhibitors with potentials for the treatment of SARS-CoV-2. However, the only dexamethasone has attractive pharmacokinetic and toxicity properties probable for drug development; therefore, our study provides a basis for developing efective drugs targeting a specifc protein in the SARS-CoV-2 life cycle.

Keywords SARS-COV-2 · Trial drugs · CLpro · RdRp · Safety

Introduction death recorded (WHO 2020). The report has it that three categories of people i.e. children, aged, and those with The novel SAR-COV-2 outbreak has resulted in almost half a underlying medical history/low immunity (Shyamala et al. million death across the globe (Qamar et al. 2020). Between 2020) are most vulnerable to the disease. Consequently, December 2019 and June 2020, more than 9473,215 per- many advanced nations of the world are now epicenters for sons have been infected and 484,249 number of death has the disease with no current approved cure (Shyamala et al. been reported globally (WHO 2020). In sub-Sahara Africa, 2020). The current management strategy only involves the Nigeria in particular, thirty-six states including the Federal provision of symptomatic relief to patients (Shyamala et al. Capital Territory (FCT) have recorded cases of infected 2020). patients, with more than 22,614 already infected and 549 The COVID-19 virus which causes severe acute res- piratory syndrome (SARS) in humans is a positive-strand RNA virus that shares 80% homology with SAR-CoV * Banjo Semire and about 96% identity with bat coronavirus Bat CoV [email protected] Rat G13 (Zhou et al. 2020). The genomic structure of the 1 Department of Biochemistry, Faculty of Basic Medical virus is a 5’-leader-UTR replicase-S(Spike)-E(Envelop)- Sciences, Ladoke Akintola University of Technology, M(Membrane)-N(Nucleocapsid)-3’ÚTR poly (A) tail, Ogbomoso, Nigeria with the accessory genes responsible for viral pathogenesis 2 Department of Pure and Applied Chemistry, Faculty interspersed within the structural genes at the 3’ end of the of Pure