Tamarind (Tamarindus indica L.) Seed a Candidate Protein Source with Potential for Combating SARS-CoV-2 Infection in Obesity

Abstract

Introduction:: Obesity and coronavirus disease (COVID)-19 are overlapping pandemics, and one might worsen the other.

Methods:: This narrative review discusses one of the primary mechanisms to initiate acute respiratory distress syndrome, uncontrolled systemic inflammation in COVID-19, and presents a potential candidate for adjuvant treatment. Blocking the S protein binding to angiotensin-converting enzyme 2 (ACE-2) and the 3C-like protease (3CL ^pro) is an effective strategy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Results:: Host proteases such as FURIN, trypsin, and transmembrane serine protease 2 (TMPRSS) act in S protein activation. Tamarind trypsin inhibitor (TTI) shows several beneficial effects on the reduction of inflammatory markers (tumor necrosis factor α [TNF-α], leptin) and biochemical parameters (fasting glycemia, triglycerides, and very low-density lipoprotein [VLDL]), in addition to improving pancreatic function and mucosal integrity in an obesity model. TTI may inhibit the action of proteases that collaborate with SARS-CoV-2 infection and the neutrophil activity characteristic of lung injury promoted by the virus.

Conclusion:: Thus, TTI may contribute to combating two severe overlapping problems with high cost and social complex implications, obesity and COVID-19.

Fig. 1-. Obesity and associated comorbidities as risk factors for complications from SARS-CoV-2 infection, and hypothesis of the TTI mechanism of action. Obesity affects several organs, which have several responses, such as increased inflammation, changes in sensitivity and the action of hormones, dyslipidemia, and others. This metabolic deregulation favors increased expression of ACE-2, which is cleaved in the C-terminal segment by proteases such as TMPRSS2 and FURIN, and there is activation of the spike glycoprotein, so this process facilitates the entry of SARS-CoV-2 into the cells, causing viral infection. Also, 3CL ^pro is considered a key component in polyprotein processing and plays an important role in the replication and transcription of viral RNA. The TTI effects in in vitro and preclinical studies show several antiobesity and anti-inflammatory effects and appear to be possible inhibitors of the proteases TMPRSS2, FURIN, and 3CL^pro.

ACE-2 = angiotensin-converting enzyme 2; CCK = cholecystokinin; FURIN = member of the mammalian prohormone-protein convertases family; HNE = human neutrophil elastase; IL-1β = interleukin 1-β; LPS = lipopolysaccharide; MCP-1 = monocyte chemoattractant protein 1; SREBP = sterol regulatory element-binding proteins; TG = triglyceride; TMPRSS2 = transmembrane serine protease 2; TNF-α = tumor necrosis factor α; TTI = trypsin inhibitor from tamarind; VLDL-c = very-low-density lipoprotein cholesterol; 3CL ^pro = 3C-like protease.