DEVELOPMENT OF POTENTIAL DRUG CANDIDATES FOR SARS-CoV-2 USING MOLECULAR HYBRIDIZATION APPROACH

Abstract

ABSTRACT In December 2019, an unknown viral infection originated from a local fish and wild animal market in Wuhan city, China. Since then, the virus has rapidly spread across mainland China followed by the rest of the world. On February 11, 2020, the World Health Organization (WHO), identified the virus as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In March 2020, WHO declared the coronavirus outbreak a global pandemic. As of March 2022, SARS-CoV-2 has affected about 500 million people with over 6 million deaths worldwide. Although the world has survived numerous pandemics in the past, this one is an unprecedented global health challenge that has greatly impacted our lives and the socioeconomic of the world. At present therapeutic options for SARS-CoV-2 are very limited. Researchers adopting various approaches to develop new drug candidates for SARS-CoV-2 and the drug repurposing approach is one of them. We adopted the molecular hybridization approach to overcome the limitations of repurposing drugs. We designed and synthesized a new set of small molecules using a quinoline scaffold (from hydroxychloroquine and chloroquine), indole nucleus (from umifenovir), and rhodamine (a very well-investigated medicinally important moiety) via an optimized multistep synthetic route. All the synthesized molecules were characterized by analytical spectral studies. All the synthesized conjugates were screened against the SAR-CoV-2 virus and their cytotoxicity was determined. Computational studies were carried out to validate the biological data. Some synthesized compounds showed promising anti-viral properties against SAR-CoV-2.