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.

Despite the huge loss of lives and massive disruption of the world economy by the COVID-19 pandemic caused by SARS-CoV-2, scientists are yet to come out with an effective therapeutic against this viral disease. Several vaccines have obtained ‘emergency approval’, but difficulties are being faced in the even distribution of vaccines amongst high- and lowincome countries. On top of it, comorbidities associated with COVID-19 like diabetes, hypertension and malaria can seriously impede the treatment of the main disease, thus increasing the fatality rate. This is more so in the context of sub-Saharan African and south Asian countries. Our objective was to demonstrate that a single plant containing different phytoconstituents may be used for treatment of COVID-19 and comorbidities. Towards initial selection of a plant, existing scientific literature was scanned for reported relevant traditional uses, phytochemicals and pharmacological activities of a number of plants and their phytoconstituents pertaining to treatment of COVID-19 symptoms and comorbidities. Molecular docking studies were then performed with phytochemicals of the selected plant and SARS-CoV-2 components – Mpro, and spike protein receptor binding domain and hACE2 interface using AutoDock Vina. We showed that crude extracts of an indigenous African plant, Costus afer having traditional antidiabetic and antimalarial uses, has phytochemicals with high binding affinities for Mpro, and/or spike protein receptor binding domain and hACE2 interface; the various phytochemicals with predicted high binding energies include aferoside C, dibutyl phthalate, nerolidol, suginal, and ±-terpinene, making them potential therapeutics for COVID-19. The results suggest that crude extracts and phytochemicals of C. afer can function as a treatment modality for COVID-19 and comorbidities like especially diabetes and malaria.