Executive Summary : | The SARS-CoV-2 outbreak has spread globally, causing fear due to its evolution into multiple infectious variants. The COVID-19 pandemic has led to the emergence of variants with improved viral fitness, immunological evasion, and transmissibility. The need for effective treatments against all SARS-CoV-2 variants is urgent, as none of the vaccines have been effective against the Omicron variant and its subvariants. Some variants, such as the B.1.351 variant in South Africa, have mutations in the spike protein, which could reduce the effectiveness of monoclonal antibody-based therapies and the neutralizing activity of some COVID-19 vaccines. The Omicron variant, first identified in South Africa in November 2021, has been of concern due to its high number of mutations in the virus spike protein. Operating monitoring and research are needed to understand the full impact of Omicron or current SARS-CoV-2 variants on the COVID-19 pandemic. Acute preventive measures are required to tackle the emergence of deadly future variants. Previous studies have designed peptide therapeutics that can inhibit wild SARS-CoV-2 spike function, and a modified peptide therapeutic has been designed to inhibit not only the wild spike but also the most lethal Delta and Omicron variants. This proposal aims to predict all possible future virus variants using state-of-the-art computational methods and artificial intelligence (AI). It also proposes the design of potent therapeutics against existing and incoming SARS-CoV-2 variants. Validating computational predictions will involve isothermal calorimetry, fluorescence, NMR-based binding assay, and other experiments for deleterious variants and potent neutralizing molecules/therapeutics. |