CNPD CONFERENCE 2021: Dr Ismail Nature vs. artificial intelligence guided synthesis against COVID19

Natural products vs. rational drug designed molecules against SarsCoV-2 targets: Nature vs. artificial intelligence guided synthesis
Fyaz Ismail
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK

The current Covid-19 pandemic has mobilized both the pharma sector and government-industry-academic partnerships to rapidly-produce effective vaccines, currently able to diminish the severity of against SARS-CoV-2 infections. Protection in clinical studies has ranged from 95% for mRNA vaccines to ~70% for adenovirus-based vaccines diminishing severity of infections and hospitalizations. Apart from vaccine sceptics, in some patients vaccines may be contraindicated, or ineffective due to the appearance of resistant mutants virus strains. Since high resolution atomic resolution cryo-em structures of SARS-CoV-2 virus target proteins are publicly available in protein databases, rational drug design of viral proteases covalent inhibitors, especially 3ClPro has accelerated [2]. For instance, the oral antiviral clinical candidate PF-07321332 (Fig. 1a), a SARS-CoV2-3CL protease inhibitor, reveals potent anti-viral activity in vitro against SARS-CoV-2, as well as activity against other coronaviruses [3].
Synthetic compounds surveyed from published work range from weakly active lead compounds to those that could serve as clinically useful compounds [1]. In parallel, various natural products have also been screened mostly in vitro and in silico (against protein targets) providing a wealth of information. Consequently, promising compounds including will be highlighted [2], together with synthetic compounds which appear promising, such as metaquine; as lead compounds which we are developing in conjunction with Brazilian colleagues [5] and The Oswaldo Cruz Foundation, Brazil against resistant variants of SarsCoV2.

Cite as: Ismail, Fyaz. 2021. Natural products vs. rational drug designed molecules against SarsCoV-2 targets: Nature vs. artificial intelligence guided synthesis., Centre for Natural Products Discovery, Liverpool John Moores University, Liverpool, 13-14 May.