Plant Products as Inhibitors of Coronavirus 3CL Protease

Abstract

Background: The ongoing COVID-19 pandemic has created an alarming situation due to extensive loss of human lives and economy, posing enormous threat to global health security. Till date, no antiviral drug or vaccine against SARS-CoV-2 has reached the market, although a number of clinical trials are under way. The viral 3-chymotrypsin-like cysteine protease (3CLpro), playing pivotal roles in coronavirus replication and polyprotein processing, is essential for its life cycle. In fact, 3CLpro is already a proven drug discovery target for SARS- and MERS-CoVs. This underlines the importance of 3CL protease in the design of potent drugs against COVID-19.Methods: We have collected one hundred twenty-seven relevant literatures to prepare the review article. PubMed, Google Scholar and other scientific search engines were used to collect the literature based on keywords, like “SARS-CoVs-3CL protease,” “medicinal plant and anti-SARS-CoVs-3CL protease” published during 2003–2020. However, earlier publications related to this topic are also cited for necessary illustration and discussion. Repetitive articles and non-English studies were excluded.Results: From the literature search, we have enlisted medicinal plants reported to inhibit coronavirus 3CL protease. Some of the plants like Isatis tinctoria L. (syn. Isatis indigotica Fort.), Torreya nucifera (L.) Siebold and Zucc., Psoralea corylifolia L., and Rheum palmatum L. have exhibited strong anti-3CLpro activity. We have also discussed about the phytochemicals with encouraging antiviral activity, such as, bavachinin, psoralidin, betulinic acid, curcumin and hinokinin, isolated from traditional medicinal plants.Conclusion: Currently, searching for a plant-derived novel drug with better therapeutic index is highly desirable due to lack of specific treatment for SARS-CoV-2. It is expected that in-depth evaluation of medicinally important plants would reveal new molecules with significant potential to inhibit coronavirus 3CL protease for development into approved antiviral drug against COVID-19 in future.

Herbal medicine use for the management of COVID-19: A review article

“…Clinical trials of a few herbal compounds against SARS-CoV-2-3CL Pro aroused hope for plant-derived anti -SARS-CoV-2 drugs. Very recently, 3CL protease inhibitor NLC-001, a plant product administered orally as a dietary supplement, got US FDA approval [ 61 ].…”

Drugs repurposing against SARS-CoV2 and the new variant B.1.1.7 (alpha strain) targeting the spike protein: molecular docking and simulation studies

“…The primary purpose of this manuscript is to disseminate some knowledge about necessary drugs which could be used subject to trial results. Previous studies mainly report terpenes [ 65 ], phytomedicine [ 66 ], extracts from spices [ 67 ], marine products [ 68 ], plants secondary metabolites and various other forms of drugs as potential candidates as SARS CoV-2 inhibitors [ 69 ].…”

Brief survey on phytochemicals to prevent COVID-19

“…Urtica dioica agglutinin (UDA) an active compound derived from the Urtica dioica plant species which prevents the viral attachment to cell through binding with the glycoprotein of SARS-CoV virus [ 52 ]. Earlier study suggested that traditional Chinese medicinal (TCM) plans Scutellaria baicalensis Georgi, used globally as a broad spectrum antiviral compound, which also have the anti-Covid-19 3CL pro activity in in-vitro study [ 53 ]. Luteolin (flavonoid) and resveratrol (terpenoid) are extracted from Veronica linariifolia plants and strongly inhibited entry of coronavirus by interfering with spike protein and ACE2 receptor of SARS-CoV [ 53 , 54 ].…”