Natural Bioactive Compounds from Fungi as Potential Candidates for Protease Inhibitors and Immunomodulators to Apply for Coronaviruses

Abstract

The inhibition of viral protease is an important target in antiviral drug discovery and development. To date, protease inhibitor drugs, especially HIV-1 protease inhibitors, have been available for human clinical use in the treatment of coronaviruses. However, these drugs can have adverse side effects and they can become ineffective due to eventual drug resistance. Thus, the search for natural bioactive compounds that were obtained from bio-resources that exert inhibitory capabilities against HIV-1 protease activity is of great interest. Fungi are a source of natural bioactive compounds that offer therapeutic potential in the prevention of viral diseases and for the improvement of human immunomodulation. Here, we made a brief review of the current findings on fungi as producers of protease inhibitors and studies on the relevant candidate fungal bioactive compounds that can offer immunomodulatory activities as potential therapeutic agents of coronaviruses in the future.

Could Ergothioneine Aid in the Treatment of Coronavirus Patients?

“…To date, no studies have looked at the potential of ET to directly inhibit coronavirus replication. A recent review by Suwannarach et al [ 106 ] highlights the potential for fungal extracts, of which a major active component is ET, to demonstrate inhibitory activity on other RNA viruses such as HIV-1 and suggests a possible application for the inhibition of binding or replication of coronaviruses. Likewise, Xiao et al [ 107 ] demonstrated that pure ET was able to dose-dependently inhibit the pro-fs (human immunodeficiency virus-1 protein; HIV-1) activation of the HIV long terminal repeat region (which serves as a promoter‒enhancer for viral genome integration in host DNA) using an in vitro assay, suggesting that ET directly inhibits HIV transcription.…”

The recent challenges of highly contagious COVID‐19, causing respiratory infections: Symptoms, diagnosis, transmission, possible vaccines, animal models, and immunotherapy

“…Łoczechin et al, 2019 have reported the antiviral activity of seven different CQDs for the treatment of human coronavirus infections. In addition, Suwannarach et al., 2020 have also studied the immunomodulatory activities of fungal bioactive compounds as potential therapeutic agents against CoV. Liu, Zhou, et al, 2020 have discussed some patents disclose methodologies for treating and preventing CoV infections, which may be applicable to COVID‐19.…”

Natural products as home‐based prophylactic and symptom management agents in the setting of COVID‐19

“…Medicinal mushrooms are an untapped resource which show potential antiviral, antiinflammatory, and immunomodulatory properties against various viruses like HSV, EBV hepatitis C virus, (HCV), human immunodeficiency virus (HIV), H1N1 strain of flu, and influenza (Ellan et al, 2019;Linnakoski et al, 2018;Muszy nska, Grzywacz-Kisielewska, Kała, & Gdula-Argasi nska, 2018). The secondary metabolites from these mushrooms such as alkaloids, non-ribosomal peptides, polyketides, and terpenoids have shown protease inhibitory activities against HIV-1 and hepatitis C virus (El-Fakharany, Haroun, Ng, & Redwan, 2010;Sato et al, 2009;Sillapachaiyaporn et al, 2019 (Lu et al, 2020;Ying et al, 2016) might also have protease inhibitory activities against the SARS-CoV-2 papain-like protease (Suwannarach et al, 2020). These mushroom extracts have bioactive polysaccharides (β-glucans) and galactomannan that are known to have immunomodulatory properties and stimulate the production of antiviral cytokines such as TNF-α, NK-cells, and macrophages (Jung et al, 2019).…”