Table 1.

Phytomolecules reported to possess antiviral activity against other enveloped and respiratory viruses as well as their immunomodulatory activity for potential repurposing for treatment and prophylaxis of SARS-CoV-2

Phytomolecule	Class of compound	Source plant	Traditional uses of source plant	Anti-viral activity of phytomolecule	Immunomodulatory activity of phytomolecule aiding in anti-viral activity
Baicalin	Flavonoid	Scutellaria baicalensis Georgi	Used in TCM as an anti-pyretic [62], and for the treatment of pharyngitis, pneumonia, and upper respiratory infections [63]	Enveloped viruses—dengue (DENV) influenza virus, A/PR/8/34 (H1N1) [64]	In vitro inhibition of chemokine binding to human leukocytes, induction of IFN-γ critical for innate, and adaptive immunity against viral pathogens [65]
Rhein	Anthraquinone	Rheum palmatum L	Prescribed in TCM for the treatment of cough, jaundice, and hepatitis [66]	IAV [67]	Activation of TLR4, Akt, p38, JNK MAPK, and NF-κB pathways [67]
Chebulagic acid, punicalagin	Tannin	Terminalia chebula Retz	Fruits commonly used to treat digestive disorders, chronic cough, sore throat, and asthma [68], used for recovery from acute respiratory infections	IAV, HIV-1 [69], HSV-1, RSV, HCV, CMV [70]	COX-LOX dual inhibitor, increased IL-2, IL-10 TNF-α, antioxidant enzyme levels, elevated T and B cell proliferation [71]
Andrographolide	Terpenoid	Andrographis paniculata (Burm.f.) Wall. ex Nees	Used for treatment of upper respiratory infections, bronchitis, inflammation [72]	DENV-2 and DENV-4 strains in vitro, HSV, HBV, HCV, HIV, CHIKV [73]	Effective enhancement of cytotoxic T cells, natural killer (NK) cells, phagocytosis, antibody-dependent cell-mediated cytotoxicity (ADCC) [74], significant stimulation of antibodies, and delayed type hypersensitivity (DTH) response [75], increased proliferation of lymphocytes, and production of IL-2, TNF-α, and CD marker expression
Glycyrrhizin	Terpene	Glycyrrhiza glabra L	Used in TCM for treatment of respiratory tract disorders, cough, asthma, sore throat [76], eliminating phlegm, and providing cough relief [77]	Influenza A virus, H5N1, H1N1, hepatitis C virus, HIV, rotavirus, Newcastle disease virus [78]	Upregulated expression of CD40, CD86, MHC-II maturation markers on dendritic cells, enhanced production of IL-2 by dendritic cells, IFN-γ, IL-10, and enhanced allogeneic T cell proliferation, reduction in IL-4 production, stimulation of endogenous interferon production, elevated anti-oxidant status, and decreased incidence of free-radical induced lipid peroxidation [79, 80]
Betulinic acid	Terpene	Ziziphus jujuba Mill.and Syzigium claviflorum (Roxb.) Wall.ex A.M.Cowan & Cowan	Used in treatment of respiratory infections	HSV-2, HIV-1, IAV in vitro [81]	Increased levels of TNF-α from peritoneal macrophages, IL-12, CD4 +, and lymphocyte population along with enhanced thymus and spleen indices, decreased levels of IL-10 and TGF-β along with increased IgG production. Downregulation of IFN-γ levels [82, 83]