Our preliminary Molecular Docking study suggested that the triazole containing bases shows strong interaction and binding effect reflecting their activity to stop the extension of RNA of the viruses. The target nucleosides are believed to have mechanism of action which is similar to Avigan. This work would yield a highly effective COVID-19 drug.

PUBLICATIONS

1. ● A Systematic Review of the Efficacy and Safety of Favipiravir (Avigan) for the Treatment of Novel COVID-19 Infections ●Bag*, Subhendu Sekhar; Sinha, Sayantan; and Saito, Isao  ● Medical Research Archives 2020, XX, XX (In Press).

2. Bag*, S. S; Sinha S. S. Uncovering Potent Inhibitory Activity of Our Reported Unnatural Triazolyl Nucleobase Analogues Against SARS-CoV-2 RdRp: An In Silico Study (Communicated).

3.  Bag*, S. S; Sinha S. S.; Saito, I. Proposed Avigan Analoguous Unnatural Triazolyl Nucleosides as Potent Inhibitors of SARS-CoV-2 RdRp: An In Silico Study (Communicated).

5.  Bag*, S. S.;  Sinha S. S. A Systematic Review of the Efficacy and Safety of Remdesivir for the Treatment of Novel COVID-19 Infections (Communicated).

6. ● SARS-CoV-2 from Host Cell Entry, Pathogenicity to Possible Remediation of the Infection Caused: An Overview● Bag*, Subhendu Sekhar and Sinha, Sayantan●  2020, XX, XX (Communicated).

We have recently submitted a proposal to CSIR for funding based on "Design, Synthesis and Therapeutic Application of Novel Peptidomimetic Inhibitor Drugs (PIDs) for COVID-19". Our design of peptidomimetic drug inhibitor (PID) against SARS-CoV-2 M^pro main protease is proposed to starts from a knowledge of substrate binding pocket, substrate and mechanism of action of the potent inhibitors N3 and a-ketoamide based peptidic inhibitor. This understanding is a starting point for the development of new SARS-CoV-2 M^pro inhibitors. We propose that the variation of P1/P2 in our design would lead to potent N3-analog and a-keto amide inhibitor, respectively. Initially we want to choose our unnatural triazolyl aliphatic amino acid scaffold (^AlTAA) to construct our inhibitor. It is a β-Ala-Gly dipeptide mimic and when present in the backbone of a Leu-Enkephalin analog sequence, it induces β-turn structure, thus acting as β-turn-nucleator.

As the SAR-CoV-2 Mpro specifically cleave the peptide bond following a P1-glutamine residue we decided to use a 5-membered triazolyl ring which can be a mimic of amide side chain of glutamine (which can be called as Gln-Tz). This triazole moiety can enhance the power of the inhibitors possibly due to rigid triazole ring which would lead to a reduction of the loss of entropy upon binding to the target protease.

PUBLICATIONS

1.  Bag*, S. S; Sinha S. S. Uncovering Potent Inhibitory Activity of Our Reported Peptidomimetic Designs Against SARS-CoV-2 M^pro : An In Silico Study  (Communicated).

The Proposed concept (A) SARS-CoV-2 binds to the HSPG receptor on the host cell and scans the cell surface to locate its specific hACE2 entry receptor (B) The HSPG mimicking biogenic CQD bind to the S glycoprotein of SARS-CoV-2 and thereby stops infection of host cell. Also the material is expected to bind to the catalytic site of viral RdRp protein and the screened natural RdRp inhibiting molecules coated onto the material surface restricts the activity of RdRp and hence can stop viral replication.

PUBLICATIONS

1.  ● Inhibiting the Pathogenicity of SARS-CoV-2 with a Designer Fluorescent Carbon Quantum Dot (FL-ASCQD): A Concept● Bag*, Subhendu Sekhar and Sinha, Sayantan● 2020, XX, XX (Under Review).  

Binding of (A) wedelolactone (B) luteolin and (C) apigenin in the catalytic site of nCoV-19 RdRp. Interaction of (D) wedelolactone,  (E) luteolin and (F) apigeninwith with amino acids in the active site of the catalytic pocket

Anti-SARS-CoV-2 Nanomedicine: The material is an antiviral biogenic fluorescent Carbon Quantum Dot (FL-^ASC_QD), the surface decorated with Angiotensin II which is the primary substrate for human angiotensin-converting enzyme 2 (hACE2) receptors (a receptor that is utilized by nCoV-19 for host cell entry). In addition, the sulfate-decorated surface would act as a mimic of heparan sulfate proteoglycan (HSPG) receptors of the host cell. Therefore,  in the presence of novel coronavirus, the chemically modified nanomedicine would act as a competitive binder of hACE2 receptor. Thus,  it would serve as a decoy to block all possible routes for entry into the cells. So if the virus cannot locate its cellular entry receptor (hACE2), there will be no chance of infection. Additionally, the viral spiked glycoproteins will attach to the HSPG mimics, and hence detection will be possible through photo-physical studies. Finally, the generic antiviral property of the nanomedicine will restrict the RNA dependent RNA polymerase (RdRp) activity and hence stop viral replication.

PUBLICATIONS

This idea has been well appreciated and selected amongst the top ideas in the "Undo Corona Ideation Challenge," organized by Government of Assam.

Three Problems-One Solution: Photocatalytic Treatment of Wastewater Containing SARS-CoV-2, Antibiotics and MDR Bacteria

PUBLICATIONS

1.  ●Wastewater an Emerging Source of Spreading COVID-19 Infections in India: A Recent Perspective● Bag*, Subhendu Sekhar; and Sinha, Sayantan● Current Science 2020, XX, XX (Under Review).

Fluorescent Antimicrobial Peptide-based Bacteria/Virus Sensor: We are now engaged  in developing bioinspired materials and antimicrobial peptide based biomaterial for possible clinical use. We are engaged in creating new and novel therapeutic alternatives against the recent rise of multidrug-resistant microbial strains. We have put up a project proposal based on the recent call for Team Science Grant & Clinical/Public Health Research Centres Grants from IndiaAlliance DBT. We want to exploit the β-turn/β-sheet Peptidomimetics developed by Dr. Bag, Peptoids by Prof. Aaron and the Surface tethering techniques by Prof. Lalit at BSBE Department of IITG to create therapeutic surfaces. The bioinspired materials based on fluorescent peptidomimetics developed by me could also find applications in sensing and medical diagnostic purposes. This project would have great impact to resist virus protein capsids, such as SARS-CoV-2 and similar SARS viruses, from surface attachment.