Pharmacological hypothesis: TPC2 antagonist tetrandrine as a potential therapeutic agent for COVID‐19

Abstract

We wish to draw attention to the possibility of repurposing the existing calcium channel blocking drug tetrandrine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Tetrandrine is a bisbenzylisoquinoline that can be extracted from the perennial vine plant Stephania tetrandra S Moore (Chinese patent WO2004009106A1, 2002), which has been used in traditional Chinese medicine (TCM) (1-3, and references therein). It can also be synthesized chemically (US Patent 10,023,584 B2, 2018 4). There is extensive literature on the potential anti-inflammatory, immunosuppressive, oncological, and cardiovascular effects of tetrandrine. 2,5-7 It is licensed in China for the treatment of silicosis, but to our knowledge has not been licensed for viral illnesses in any country to date.

Current Updates on Naturally Occurring Compounds Recognizing SARS-CoV-2 Druggable Targets

“…According to Riva et al, hanfangchin A , also called tetrandrine (TET) ( Figure 6 ), showed dose-dependent antiviral activities [ 82 , 83 ]. TET is a benzyltetrahydroisoquinoline alkaloid isolated from the root of the plant Stephania tetrandra with several pharmacological effects [ 84 ].…”

“…It was hypothesized that TET could work by blocking the two-pore channel 2 (TPC2) located in the membranes of host endolysosomal compartments by which SARS-CoV-2 can egress from these organelles and continue its replication [ 83 , 85 ].…”

“…Currently, severa trials for resveratrol are undergoing (NCT04542993, NCT04536090, and NCT043 2.1.6. Hanfangchin A According to Riva et al, hanfangchin A, also called tetrandrine (TET) (F showed dose-dependent antiviral activities [82,83]. TET is a benzyltetrahydroisoq alkaloid isolated from the root of the plant Stephania tetrandra with several phar ical effects [84].…”

“…Structurally, two benzyl-tetrahydroisoquinolines are connected linkages to form tetrandrine with tetrahydroisoquinoline N-methylation, beari regular eighteen-member ring [85]. It was hypothesized that TET could work by blocking the two-pore channel located in the membranes of host endolysosomal compartments by which SAR can egress from these organelles and continue its replication [83,85].…”

“…Glycyrrhizin, an active component of liquorice roots, was investigated again CoV-2 ( Figure 7). Combining high throughput screening (HTS) and comp It was hypothesized that TET could work by blocking the two-pore channel 2 (TPC2) located in the membranes of host endolysosomal compartments by which SARS-CoV-2 can egress from these organelles and continue its replication [83,85].…”