ABSTRACT
Coronavirus disease (COVID-19) can cause critical conditions that require efficient therapeutics. Several medicines are derived from plants, and researchers are seeking natural compounds to ameliorate the symptoms of COVID-19. Viral enzymes are popular targets of antiviral medicines; the genome of coronaviruses encodes several enzymes, including RNA-dependent RNA polymerase and viral proteases. Various screening systems have been developed to identify potential inhibitors. In this review, we describe the natural compounds that have been shown to exert inhibitory effects on coronavirus enzymes. Although computer-aided molecular structural studies have predicted several antiviral compound candidates, the current review focuses on experimentally proven natural compounds.
Subject(s)
Antiviral Agents/pharmacology , COVID-19 Drug Treatment , Enzyme Inhibitors , Phytochemicals/pharmacology , Enzyme Inhibitors/pharmacology , Humans , RNA-Dependent RNA Polymerase/antagonists & inhibitors , SARS-CoV-2/drug effects , SARS-CoV-2/enzymologyABSTRACT
The COVID-19 pandemic has resulted in a huge number of deaths from 2020 to 2021; however, effective antiviral drugs against SARS-CoV-2 are currently under development. Recent studies have demonstrated that green tea polyphenols, particularly EGCG, inhibit coronavirus enzymes as well as coronavirus replication in vitro. Herein, we examined the inhibitory effect of green tea polyphenols on coronavirus replication in a mouse model. We used epigallocatechin gallate (EGCG) and green tea polyphenols containing more than 60% catechin (GTP60) and human coronavirus OC43 (HCoV-OC43) as a surrogate for SARS-CoV-2. Scanning electron microscopy analysis results showed that HCoV-OC43 infection resulted in virion particle production in infected cells. EGCG and GTP60 treatment reduced coronavirus protein and virus production in the cells. Finally, EGCG- and GTP60-fed mice exhibited reduced levels of coronavirus RNA in mouse lungs. These results demonstrate that green tea polyphenol treatment is effective in decreasing the level of coronavirus in vivo.
Subject(s)
Antiviral Agents/pharmacology , Catechin/analogs & derivatives , Coronavirus Infections/drug therapy , Polyphenols/pharmacology , Tea/chemistry , Virus Replication/drug effects , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Catechin/pharmacology , Catechin/therapeutic use , Cell Line , Coronavirus Infections/virology , Coronavirus OC43, Human/drug effects , Coronavirus OC43, Human/physiology , Disease Models, Animal , Humans , Mice , Polyphenols/chemistry , Polyphenols/therapeutic useABSTRACT
Epigallocatechin gallate (EGCG) is a major catechin found in green tea, and there is mounting evidence that EGCG is potentially useful for the treatment of coronavirus diseases, including coronavirus disease 2019 (COVID-19). Coronaviruses encode polyproteins that are cleaved by 3CL protease (the main protease) for maturation. Therefore, 3CL protease is regarded as the main target of antivirals against coronaviruses. EGCG is a major constituent of brewed green tea, and several studies have reported that EGCG inhibits the enzymatic activity of the coronavirus 3CL protease. Moreover, EGCG has been reported to regulate other potential targets, such as RNA-dependent RNA polymerase and the viral spike protein. Finally, recent studies have demonstrated that EGCG treatment interferes with the replication of coronavirus. In addition, the bioavailability of EGCG and future research prospects are discussed.
ABSTRACT
COVID-19 pandemic results in record high deaths in many countries. Although a vaccine for SARS-CoV-2 is now available, effective antiviral drugs to treat coronavirus diseases are not available yet. Recently, EGCG, a green tea polyphenol, was reported to inhibit SARS-CoV-2 3CL-protease, however the effect of EGCG on coronavirus replication is unknown. In this report, human coronavirus HCoV-OC43 (beta coronavirus) and HCoV-229E (alpha coronavirus) were used to examine the effect of EGCG on coronavirus. EGCG treatment decreases 3CL-protease activity of HCoV-OC43 and HCoV-229E. Moreover, EGCG treatment decreased HCoV-OC43-induced cytotoxicity. Finally, we found that EGCG treatment decreased the levels of coronavirus RNA and protein in infected cell media. These results indicate that EGCG inhibits coronavirus replication.
Subject(s)
Coronavirus 229E, Human/drug effects , Coronavirus OC43, Human/drug effects , Polyphenols/pharmacology , Tea/chemistry , Virus Replication/drug effects , Amino Acid Sequence , Cell Line, Tumor , Coronavirus 229E, Human/physiology , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus OC43, Human/physiology , Humans , SARS-CoV-2/drug effects , SARS-CoV-2/physiologyABSTRACT
COVID-19, a global pandemic, has caused over 750,000 deaths worldwide as of August 2020. A vaccine or remedy for SARS-CoV-2, the virus responsible for COVID-19, is necessary to slow down the spread and lethality of COVID-19. However, there is currently no effective treatment available against SARS-CoV-2. In this report, we demonstrated that EGCG and theaflavin, the main active ingredients of green tea and black tea, respectively, are potentially effective to inhibit SARS-CoV-2 activity. Coronaviruses require the 3CL-protease for the cleavage of its polyprotein to make individual proteins functional. EGCG and theaflavin showed inhibitory activity against the SARS-CoV-2 3CL-protease in a dose-dependent manner, and the half inhibitory concentration (IC50) was 7.58 µg/ml for EGCG and 8.44 µg/ml for theaflavin. In addition, we did not observe any cytotoxicity for either EGCG or theaflavin at the concentrations tested up to 40 µg/ml in HEK293T cells. These results suggest that upon further study, EGCG and theaflavin can be potentially useful to treat COVID-19.