Abstract

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been identified as the agent responsible for COVID-19 pandemic. Currently, no therapeutic agents have proven effective in combating the virus. Managing the infection is mainly palliative in nature, involving infection prevention strategies and supportive therapy anchored on drugs that practitioners have had previous usage experience. Previously exploited therapeutic agents include antiviral and antimalarial agents (remdesivir, hydroxychloroquine, chloroquine, lopinavir, umifenovir, favipiravir, and oseltamivir). Micronutrients (zinc, selenium) have also been used. There are claims of herbal preparations that are thought to be beneficial. The self-formulated herbal preparation, COVI-MXG contains a unique combination of five plants. In silico methodologies were used to evaluate the phytochemical constituents. This was to determine possible antiviral activity, safety during usage and pharmacokinetic properties. Docking studies of selected phytochemical compounds in COVI-MXG evaluated against the COVID-19 viral protein target showed binding affinity ranging from -8.1 to -4.2 Kcal/mol. Blood brain barrier permeability and gastrointestinal absorption rates varied to different degrees. Toxicity class varied from 3 to 5. LD⁵⁰ values were relatively high. COVI-MXG contained phytochemical compounds with better binding affinities for SARS-CoV-2 protein (7BV2) than currently employed therapeutic agents (remdesivivr, hydroxychloroquine, chloroquine, lopinavinavir, umifenovir, favipiravir, oseltamivir) which were included in the virtual screening. The phytochemical compounds showed excellent interactions with amino acid residues in the catalytic nsp12 domain. This excellent interaction is likely to result in a better therapeutic outcome in the management of COVID-19. In silico predictions for stability and pharmacokinetic parameters predicted that the formulation can be administered orally.

Key words: COVID-19, SAR-CoV-2, COVI-MXG, zinc.

Abbreviation

7BV2.pdb, Pdb code for crystal structure of the SARS-CoV-2 target; Arg, arginine; Asp, aspartic acid; Lys, lysine; BBB permeant, blood-brain barrier permeability; GI absorption, gastrointestinal tract absorption; COVID-19, coronavirus disease 2019; LD₅₀, lethal dose 50%; pdb, protein data bank; RNA, ribonucleic acid; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; Sdf, structure-data file; RdRp, RNA-dependent RNA polymerase.