Zingiber officinale: Ayurvedic Uses of the Plant and In Silico Binding Studies of Selected Phytochemicals With Mpro of SARS-CoV-2

Among the large number of plants that are part of the Ayurvedic system of medicine in India and Bangladesh, Zingiber officinale Roscoe (Zingiberaceae), or ginger in English, holds a special place and is often referred to as “Mahaushadha” (great medicine) and “Vishvabhesaja” (worldwide or universal herb) to signify its special status. The plant and particularly its rhizomes are used both in the raw and dry form for the relief of a multitude of disorders. Since a number of these disorders occur in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it was of interest to perform in silico studies (molecular docking) to evaluate the binding affinities of a number of constituents of Zingiber officinale with the 3C-like protease or main protease (Mpro) of SARS-CoV-2, which plays an essential role in the cleavage of viral polyproteins and subsequent viral replication. Our studies indicated that 2 of the compounds present in ginger, namely, chlorogenic acid and hesperidin, had high binding affinities for Mpro with predicted binding energies of −7.5 and −8.3 kcal/mol. The two-dimensional and three-dimensional interactions also showed that, while chlorogenic acid interacts with one of the His41 amino acids of the catalytic dyad of Mpro, hesperidin interacts with the other amino acid Cys145, which can account for their predicted high binding energies and, therefore, possibly can inhibit Mpro activity. Taken together, our findings indicate that ginger, besides alleviating the symptoms induced by SARS-CoV-2, may also play a role in inhibiting the virus.

Potential role of flavonoids against SARS-CoV-2 induced diarrhea.

COVID-19, caused by the SARS-CoV-2 virus, can lead to massive inflammation in the gastrointestinal tract causing severe clinical symptoms. SARS-CoV-2 infects lungs after binding its spike proteins with alveolar angiotensin-converting enzyme 2 (ACE2), and it also triggers inflammation in the gastrointestinal tract. SARS-CoV-2 invades the gastrointestinal tract by interacting with Toll-like receptor-4 (TLR4) that induces the expression of ACE2. The influx of ACE2 facilitates cellular binding of more SARS-CoV-2 and causes massive gastrointestinal inflammation leading to diarrhea. Diarrhea prior to COVID-19 infection or COVID-19-induced diarrhea reportedly ends up in a poor prognosis for the patient. Flavonoids are part of traditional remedies for gastrointestinal disorders. Preclinical studies show that flavonoids can prevent infectious diarrhea. Recent studies show flavonoids can inhibit the multiplication of SARS-CoV-2. In combination with vitamin D, flavonoids possibly activate nuclear factor erythroid-derived-2-related factor 2 that downregulates ACE2 expression in cells. We suggest that flavonoids have the potential to prevent SARS-CoV-2 induced diarrhea.

In silico screening of Allium cepa phytochemicals for their binding abilities to SARS and SARS-CoV-2 3C-like protease and COVID-19 human receptor ACE-2.

Corona virus SARS-CoV-2-induced viral disease (COVID-19) is a zoonotic disease that was initially transmitted from animals to humans. The virus surfaced towards the end of December 2019 in Wuhan, China where earlier SARS (Severe Acute Respiratory Syndrome) had also surfaced in 2003. Unlike SARS, SARS-CoV-2 (a close relative of the SARS virus) created a pandemic, and as of February 24 2021, caused 112,778,672 infections and 2,499,252 deaths world-wide. Despite the best efforts of scientists, no drugs against COVID-19 are yet in sight; five vaccines have received emergency approval in various countries, but it would be a difficult task to vaccinate twice the world population of 8 billion. The objective of the present study was to evaluate through in silico screening a number of phytochemicals in Allium cepa (onion) regarding their ability to bind to the main protease of COVID-19 known as the 3C-like protease or 3CLpro, (PDB ID: 6LU7), 3CLpro of SARS (PDB ID: 3M3V), and human angiotensin converting enzyme-2 (ACE-2), [PDB ID: 1R42], which functions as a receptor for entry of the virus into humans. Molecular docking (blind docking, that is docking not only against any target pocket) were done with the help of AutoDockVina. It was observed that of the twenty-two phytochemicals screened, twelve showed good binding affinities to the main protease of SARS-CoV-2. Surprisingly, the compounds also demonstrated good binding affinities to ACE-2. It is therefore very likely that the binding affinities shown by these compounds against both 3CLpro and ACE-2 merit further study for their potential use as therapeutic agents.

Challenges of COVID-19 and Tuberculosis - Urgent Need to Tackle the Dual Burden

The COVID-19 disease has currently overwhelmed all other health issues throughout the world. There can be many repercussions on existing public health issues, especially tuberculosis (TB), which is endemic in many low and middle-income countries (LMICs). In most of the LMICs, the health services are poorly equipped, the resources being diverted to control the pandemic of COVID-19, which can lead to grave consequences for LMICs. COVID-19 and TB are known to affect the respiratory system, so their symptoms are very similar, and at times can be perplexing for diagnosis. Moreover, lack of proper treatment and vaccine for COVID19 can further increase the mounting pressure. Synthetic drugs, such as hydroxychloroquine, are currently being used, but the side effects are a cause of concern. Hence, the efficacy of repositioned drugs is still under evaluation. The situation is further worsened by the possible development of drug-resistant mutants. What we need in current times is potential novel anti-viral drugs that are highly productive and economic in control and management of viral infections in LMICs. The only option which we can look upon is the natural products which are also known as bioactive compounds and their phytochemicals like flavonoids, alkaloids and peptides that have anti-viral secondary metabolites which have shown promising results on COVID-19. This review systematically emphasizes the urgency for treatment options, which can be both safe and effective, especially for TB patients from LMICs.

Evaluation of Lens culinaris phytochemicals in binding to the 3c-like protease of SARS-CoV-2 - a molecular docking approach

The novel coronavirus known as SARS-CoV-2 and the virus-induced disease COVID-19 has caused widespread concerns due to its contagiousness, fatality rate, and the absence of drug(s). This study investigated Lens culinaris and its phytochemicals, especially the flavonoids. The compounds were assessed through molecular docking studies for their binding abilities with the major protease of the novel coronavirus, SARS-CoV-2 (PDB: 6LU7). A total of 42 phytochemicals of Lens culinaris were analyzed through molecular docking studies for their binding affinities to COVID 3C-like protease. Of them, 23 compounds were found to have binding affinities to the protease of -7.5 kcal/mol or higher. Our study indicates that Lens culinaris contains a number of polyphenolic compounds as well as phytosterols, which can bind to the active site of the protease, and so merits further scientific attention on trials for use as potential anti-COVID-19 drugs.