Synthesis of Novel Halogenated Heterocyclic compounds and their uses as Target SARS-CoV-2 main Protease (Mpro) and Potential Anti-Covid-19

Abstract

Since the first appearance of the coronavirus disease-2019 (COVID-19) in Wuhan, China, in December 2019, it has been spreading globally with devastating ramifications. The lack of anti-COVID-19 treatment to date warrants urgent research into potential therapeutic targets. Virtual drug screening techniques enable the identification of novel compounds that are capable of targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro). The latter plays a fundamental role in mediating viral replication and transcription, rendering it an attractive drug target. In this study, twenty six novel halogenated, heterocyclic compounds, which can inhibit Mpro, were tested by molecular docking combined with molecular dynamics simulation. Three compounds showed the highest binding affinity to the protein active site and their binding modes coincide with that of Nelfinavir. The binding of the halogenated compounds to Mpro may inhibit the replication and transcription of SARS-CoV-2 and, ultimately, stop the virallife cycle. In times of dire need for anti-COVID-19 treatment, this study lays the groundwork for further experimental research to investigate the efficacy and potential medical uses of these compounds to treat COVID-19. Novel compounds including fused thiophene, pyrimidine and pyran derivatives were tested against human RNA N7-MTase (hRNMT) and selected viral N7-MTases such as SARS-CoV nsp14 and Vaccinia D1-D12 complex to evaluate their specificity and their molecular modeling was also studied in the aim of producing anti covid-19 target molecules.