Drug repurposing of triazoles against mucormycosis using molecular docking: A short communication.

BACKGROUND: Mucormycosis, a fungal infection caused by Rhizopus species is on the rise in COVID-19 patients as a result of their suppressed immunity. The current therapies include systemic administration of Amphotericin B. HYPOTHESIS AND METHOD: We screened several triazole broad-spectrum antifungal agents against the therapeutic target in mucormycosis using computational techniques like molecular docking and compared them with isavuconazole, an approved drug. RESULT: The study concluded that 4 triazole drugs, pramiconazole, itraconazole, posaconazole and ketoconazole were strong candidates to be further evaluated and developed as a treatment for mucormycosis. CONCLUSION: Novel topical and oral therapies could be developed from these drug leads.

Entry-inhibitory role of catechins against SARS-CoV-2 and its UK variant.

BACKGROUND: The global pandemic caused by a RNA virus capable of infecting humans and animals, has resulted in millions of deaths worldwide. Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infects the lungs, and the gastrointestinal tract to some extent. Rapid structural mutations have increased the virulence and infectivity of the virus drastically. One such mutated strain known as the UK variant has caused many deaths in the United Kingdom. HYPOTHESIS: Among several indigenous natural ingredients used for prevention and cure of many diseases, the catechins have been reported for their antiviral activity, even against SARS-CoV-2. Characteristic mutations present on the spike protein have presented the newer strain its enhanced infectivity. The spike protein helps the virus bind to ACE2 receptor of the host cell and hence is a drug target. Catechins have been reported for their entry-inhibitory activity against several viruses. METHOD: In this study, we performed molecular docking of different catechins with the wild and mutant variants of the spike protein of SARS-CoV-2. The stability of the best docked complexes was validated using molecular dynamics simulation. RESULTS: The in-silico studies show that the catechins form favourable interactions with the spike protein and can potentially impair its function. Epigallocatechin gallate (EGCG) showed the best binding among the catechins against both the strains. Both the protein-ligand complexes were stable throughout the simulation time frame. CONCLUSION: The outcomes should encourage further exploration of the antiviral activity of EGCG against SARS-CoV-2 and its variants.

A molecular docking study of EGCG and theaflavin digallate with the druggable targets of SARS-CoV-2.

BACKGROUND: COVID-19 is an infectious disease caused by a novel positive-sense single-stranded RNA coronavirus called as SARS-CoV-2. This viral disease is known to infect the respiratory system, eventually leading to pneumonia. Crystallographic studies of the viral structure reveal its mechanism of infection as well as active binding sites and the druggable targets as scope for treatment of COVID-19. HYPOTHESIS: The role of tea polyphenols in prophylaxis and treatment of COVID-19 was established in this study. STUDY DESIGN: Molecular docking interactions of tea polyphenols with some of the possible binding sites of SARS-CoV-2 were performed. MATERIALS AND METHODS: From various studies on the SARS-CoV-2 reported in the literature, we chose possible drug targets (Chymotrypsin-like protease, RNA dependant RNA polymerase, Papain like protease, Spike RBD and ACE2 receptor with spike RBD) which are vital proteins. These receptors were docked against two tea polyphenols, Epigallocatechin gallate (EGCG) from green tea and Theaflavin digallate (TF3) from black tea. These polyphenols have been previously reviewed for their antiviral activities, especially against single-stranded RNA viruses. Two antiviral drugs, Remdesivir and Favipiravir were studied for comparative docking results. RESULTS: A comparative study of docking scores and the type of interactions of EGCG, TF3 with the possible targets of COVID-19 showed that the tea polyphenols had good docking scores with significant in-silico activity. CONCLUSION: These results can provide a lead in exploring both the tea polyphenols in prophylaxis as well as treatment of COVID-19.

Antiviral activity of green tea and black tea polyphenols in prophylaxis and treatment of COVID-19: A review.

BACKGROUND: The rapid spread of novel coronavirus called SARS-CoV-2 or nCoV has caused countries all over the world to impose lockdowns and undertake stringent preventive measures. This new positive-sense single-stranded RNA strain of coronavirus spreads through droplets of saliva and nasal discharge. PURPOSE: US FDA has authorized the emergency use of Remdesivir looking at the increasing number of cases of COVID-19, however there is still no drug approved to treat COVID-19. An alternative way of treatment could be the use of naturally derived molecules with known antiviral properties. METHOD: We reviewed the antiviral activities of two polyphenols derived from tea, epigallocatechin-3-gallate (EGCG) from green tea and theaflavins from black tea. Both green tea and black tea polyphenols have been reported to exhibit antiviral activities against various viruses, especially positive-sense single-stranded RNA viruses. RESULTS: Recent studies have revealed the possible binding sites present on SARS-CoV-2 and studied their interactions with tea polyphenols. EGCG and theaflavins, especially theaflavin-3,3'-digallate (TF3) have shown a significant interaction with the receptors under consideration in this review. Some docking studies further emphasize on the activity of these polyphenols against COVID-19. CONCLUSION: This review summarizes the available reports and evidences which support the use of tea polyphenols as potential candidates in prophylaxis and treatment of COVID-19.