Life Sciences & Biotechnology
Title : | Ethnomedicinal North-Eastern Spice (Allium spp.) against Respiratory Viral Infections: Efficacy, Bioactives, and Mechanistic Insight |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Ethnopharmacology, Medicinal Plants |
Principal Investigator : | Dr. Prasenjit Manna, CSIR-North - East Institute Of Science And Technology, Jorhat, Assam |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | pmanna2012@gmail.com |
Details
Executive Summary : | Respiratory viral infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still devastating causing significant morbidity and mortality worldwide. Patients with moderate and severe SARS-CoV-2 infection have lower glutathione (GSH) and higher levels of systemic oxidative stress compared to subjects with mild infection. Glutathionylation of SARS-CoV-2 main protease (Mpro) has been found to inhibit the dimerization of Mpro leading to inhibit Mpro proteolytic activity and blocking of SARS-CoV-2 replication and cytopathic effect. The binding affinity between SARS-CoV-2 and its receptor (ACE2) was less severe when disulfide bonds of any binding partner were reduced to thiols suggesting the importance of reducing environment to prevent viral infections. The enzyme, glutathione‐S‐transferase (GST) protects cells from oxidative stress via catalyzing the conjugation of GSH with electrophiles. A higher mortality was observed among COVID-19 patients with GST gene polymorphism (GSTM1−/− genotype). Maintaining high levels of GSH is essential for anti-viral response. Supplementation with GSH precursors, like N-acetyl cysteine, α-lipoic acid, or drugs containing thiol moiety (erdosteine) has been found to improve COVID-19 pathophysiology; however, limited uses due to several side effects. Organosulfur compounds (OSCs) have been found to stimulate GSH synthesis and replenish intracellular thiol pools. Various in silico studies reported the role of OSCs in preventing SRAS-CoV-2 infection and viral replication via blocking Mpro and spike protein (SP) of SARS-CoV-2. Plants belonging to the Allium genus are well known due to rich source of OSCs. The North Eastern region of India is well known for its richness in bio-diversity. Allium species namely, Allium cepa, Allium chinense, Allium hookeri, Allium sativum, and Allium odorum are wildly cultivated perennial herbs in different North Eastern states of India. In silico studies reported the beneficial role of OSCs and flavonoids present in Allium species in preventing SARS-CoV-2 induced respiratory viral infections; however, in vitro and in vivo studies and underlying molecular mechanism remain elusive. Using SARS-CoV-2 pseudovirus and live human coronavirus OC43 (HCoV-OC43, a member of betacoronavirus 1) infected cell culture and animal models, the present proposal will examine the efficacy of selected Allium species (essential oil and solvent extracts) against respiratory viral infections. The bioactive principles in the active extracts will be investigated through its metabolite profiling, activity guided fractionation, and purification strategy using various analytical techniques (GC-MS, LC-MS, HPLC, and NMR). Mechanistic insight will be studied by immunoblotting, flow cytometry, real time PCR, ELISA, and signal silencing approaches. The scientific knowledge generated in this study will provide a lead for further development of herbal formulations to prevent respiratory viral infections. |
Co-PI: | Dr. Jatin Kalita, CSIR-North - East Institute Of Science And Technology, Jorhat, Assam-785006 |
Total Budget (INR): | 59,42,960 |
Organizations involved