Table 1:

Potential natural compounds against SARS-CoV-2 infection and COVID-19 pathogenesis (Scoring according to evidence; +++ (high confidence), ++ (moderate confidence).

Compounds	mTOR inactivation	Endolysosomes and autophagy	Anti-inflammatory	Anti-SARS-CoV-2 activity [References]	Scoring
Spermidine and spermine	Negatively regulates mTOR signaling pathway [15,78,79]	Autophagy inducer [15]	Potential anti-inflammatory [74,75]	Restricts SARS-CoV-2 infection by SKP2 modulation (in vitro) [15]	++
Resveratrol	Negatively regulates mTOR signaling pathways [85–88]	Autophagy inducer [86,230,231]	Potential anti-inflammatory [232]	MERS-CoV inhibition in vitro [49]	+++
				SARS-CoV-2 inhibition in vitro [93,94]
				Proposed for clinical trials (NCT04542993)
Phytoestrogen	Negatively regulates mTOR signaling pathways [104–106]	Autophagy inducer [103,104]	Potential anti-inflammatory [97,98,100,233]	Restricts SARS-CoV in vivo [111]	+++
				Suggested as a suppressor of COVID-19 [112,114,224,234–236]
				Estrogen therapy (NCT04539626)
Trehalose	No effect on mTOR [124]	Induces autophagy and lysosomal biogenesis by TFEB activation [120,122]	Potential anti-inflammatory [237]	Potential target against COVID-19 [238]	++
		Induces lysosomes acidification and autophagy by mucolipin-1 (TRPML1) activation to protect mycobacterium tuberculosis infection [123]
Baicalin	Negatively regulates mTOR signaling pathways [133–135]	Autophagy inducer [133]	Potential anti-inflammatory [239–241]	Suppresses COVID-19 pathological condition in vivo, in vitro [137,242–244]	+++
		Induces lysosomes acidification by promoting assembly of v-ATPase pump [132]
				Proposed for clinical trial (NCT03830684)
Curcumin	Negatively regulates mTOR signaling pathways [152–154]	Autophagy inducer [59,60]	Potential anti-inflammatory [142,143,245]	Proposed against COVID-19 [245–248]	+++
				Proposed for clinical trial against COVID-19 (NCT04353310)
Quercetin	Negatively regulates mTOR signaling pathways [161,162]	Autophagy inducer [160,161]	Potential anti-inflammatory [156,249]	Potential target against COVID-19 [168,250–253]	+++
				Proposed for clinical trial against COVID-19 (NCT04377789)
Coumarin	Negatively regulates mTOR signaling pathways [177]	Autophagy inducer [176,178]	Potential anti-inflammatory [254]	Potential target against COVID-19 (in silico) 179,180]	++
Epigallocat-echin 3-gal-late [EGCG]	Negatively regulates mTOR signaling pathways [192,194,195]	Autophagy inducer [194,255]	Potential anti-inflammatory [183,185,187,189]	Potential target against COVID-19 and Proposed as previfenon (NCT04446065) [186,256–258]	+++
Naringenin	Negatively regulates mTOR signaling pathways [217]	Autophagy inducer [217,219,259]	Potential anti-inflammatory [200,261,262]	Suppresses SARS-CoV-2 infection in vitro [221,222,263]	+++
		A blocker of Two pore channels (TPCs). TPCs are highly involved in SARS-CoV-2’s entry into cells [260]