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Virtual Screening Approaches Towards the Discovery of Toll-like Receptor 7 (TLR7) Antagonists for the Management of
Thangavelu Prabha1, Saravanan Thangavelu2, Dakshinesh Parameswaran3
1Department of Pharmaceutical Chemistry, Nandha College of Pharmacy, Affiliated with The Tamil Nadu Dr. MGR Medical University, Chennai, Erode, 638052, Tamil Nadu, India.
Background:
Rheumatoid arthritis(RA) patients prompt to have high level of TLR7, when coronavirus (CoV-2) infect to these patients, further the level of TLR7 cloud be upregulated and leads to severe condition of RA. Since, some TLR7 antagonists targeting the TLR7 protein are in the clinical trials, but yet to reach the market, and many lead to serious toxicities.
Objective:
So, we have framed a hypothesis to discover the TLR7 antagonist that may inhibit to the upregulation of TLR 7 in RA patients during the CoV-2 infection via virtual screening methodology.
Methods:
Here we have focused to discover some novel TLR7 inhibitors from the ZINC database, which may effectively inhibit TLR7. Series of virtual screening analysis lead to the discovery of three active hits.
Results And Discussion:
Among these three molecules, ZINC95412580 had a highest binding energy of -15.4273 kcal/mol against the TLR7 protein (PDB Id: 6LW1) that also showed the maximum interactions within the binding pocket. c Conclusion: Thus, the compounds discovered through the use of various software can possibly be used for the management of rheumatoid arthritis during and after COVID infection. Hence, we can conclude that these molecules might be served as the inhibitors of TLR7 upregulation.
Insights
This study identifies novel Toll-like receptor 7 (TLR7) antagonists for rheumatoid arthritis (RA) management. Virtual screening revealed potential inhibitors to mitigate TLR7 upregulation during COVID-19 infection in RA patients.
Area of Science:
- Computational drug discovery
- Molecular modeling
- Pharmacology
Background:
- Rheumatoid arthritis (RA) patients exhibit elevated Toll-like receptor 7 (TLR7) levels.
- COVID-19 infection can further upregulate TLR7, exacerbating RA severity.
- Existing TLR7 antagonists face challenges with market availability and toxicity.
Purpose of the Study:
- To discover novel TLR7 antagonists for RA management.
- To inhibit TLR7 upregulation in RA patients during COVID-19 infection.
- Utilize virtual screening methodology for drug discovery.
Main Methods:
- Virtual screening of compounds from the ZINC database.
- Identification of potential TLR7 inhibitors.
- Analysis of binding energy and molecular interactions.
Main Results:
- Three active TLR7 inhibitor hits were discovered.
- ZINC95412580 exhibited the highest binding energy (-15.4273 kcal/mol) against TLR7 (PDB ID: 6LW1).
- The top molecule demonstrated significant interactions within the TLR7 binding pocket.
Conclusions:
- Discovered compounds show potential for managing RA during and after COVID-19 infection.
- These molecules may serve as effective inhibitors of TLR7 upregulation.
- Virtual screening is a viable approach for identifying therapeutic agents.
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