The novel Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a potential factor for fatal illness and a tremendous concern for global public health. The COVID-19 pandemic has entered a dangerous new phase. In the context of drug discovery, the structurally-unique and chemically-diverse natural products have been valuable sources for drug leads. In this review, we report for potential candidates derived from natural sources with well-reportedin vitroefficacy against SARS-CoV during the last decade. Additionally, a library of 496 phenolic metabolites was subjected to a computer-aided virtual screening against the active site of the recently reported SARS-CoV Main protease (Mpro). Analysis of physicochemical properties of these natural products has been carried out and presented for all the tested phenolic metabolites. Only three of the top candidates,viz.acetylglucopetunidin (31), isoxanthohumol (32) and ellagic acid (33), which are widely available in many edible fruits, obey both Lipinski's and Veber's rules of drug-likeness and thus possess high degrees of predicted bioavailability. These natural products are suggested as potential drug candidates for the development of anti-SARS-CoV-2 therapeutics in the near future.
Concluding remarks
The rapid identification of effective therapeutic interventions against COVID-19 is a major challenging issue nowadays. Taking into consideration that the development of new synthetic drugs is a time-consuming process, so repurposing the already known medications is the most convenient choice under the current situation. Hence, natural products can provide a valuable source for the rapid drug discovey of effective as well as safe anti-SARS CoV therapeutics. As has been illustrated in the current review, and other recently published reviews, a wide array of chemically-diverse natural products have proven to be excellent candidates as anti-SARS CoV, among which phenolic derivatives, viz. flavonoids were the most reported active agents, due to their promising pharmacokinetic profiles.55
Being the most susceptible targets in CoV, both Mpro and PLpro of SARS-CoV in addition to a number of host-based proteases viz. cathepsins and furin, can be utilized for the sake of developing broad-spectrum anti-SARS CoV therapeutic agents that target multiple viral and non-viral proteins. Some phenolics such as tannins and flavonoids have exhibited a broad-spectrum activity not only against SARS-CoV but also other viruses56 Based on our findings, tPSA and molecular flexibility are the most essential descriptors that should be taken into consideration for selecting active and bioavailable phenolic compounds. The reported IC50 values of SARS natural products-inhibitors were mostly recorded in a micromolar range. However, more potent synthetic or semi-synthetic derivatives can be developed from the current scaffolds as they showed low to moderate molecular complexity. With the tremendous ongoing efforts to develop broad-spectrum antiviral therapeutics to combat coronaviruses and stop the rapid spread of COVID-19 worldwide, we hope that the current outbreak to settle down in a few months, as has been witnessed previously with SARS and MERS pandemics.
Reference & Source information: https://pubs.rsc.org/
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