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Letters in Drug Design & Discovery


ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

Computational Drug Shifting Towards Drug-Drug Conjugates and Monoclonal Antibody Conjugates in the Contradictory Excursion of Asthma

Author(s): Muhammad Naveed*, Noor-ul-Ain and Muhammad Aqib Shabbir

Volume 20, Issue 9, 2023

Published on: 12 October, 2022

Page: [1219 - 1229] Pages: 11

DOI: 10.2174/1570180819666220422114450

Price: $65


Background: Pandemic of COVID-19 has gathered up the surrounding respiratory diseases such as asthma. The need to combat asthma is an unanswerable question nowadays and about 20-30% of people are getting into the trap of asthma.

Objectives: The mechanistic involvement of GPCR receptors in the protuberant signaling pathway such as Neuropeptide S receptor 1 (NPSR1 receptor) acts as a projected entry that needs to be inhibited for the prohibition of asthma.

Methods: Exaggerative G-proteins of NPSR1 receptors are exposed as a target through GPCR modeling to point drug targeting. Three Drug-Drug Conjugates (DDCs) are designed through the combination of nine chemical compounds through methylene bridges and selection was done based on docking energy and ADMET profiling. Designation of three Monoclonal Antibody Conjugates (MACs) is expedited using single monoclonal antibodies, linked through EAAAK linkers and the best conjugate was valued based on docking energy, allergenicity, toxicity, and surface accessibility leading towards cloning and expression.

Results: The best Drug-Drug Conjugate was Fluoroquinolone and 1-Indanone conjugate which possessed -7.7 Kcal/mol docking energy, lipophilicity 6.41, water solubility 1.19e-09 mg/ml, and pharmacokinetics -8.31 cm/s, indicating it to act as best drug candidate. The best Monoclonal Antibody Conjugate was Ustekinumab and Belimumab conjugate which retained -383.1 Kcal/mol docking energy, computed as non-allergen and nontoxic.

Conclusion: The use of MACs and DDCs may prove an effective treatment for lethal diseases like asthma and the future exertion will support the in vitro synthesis delivered in this study of conjugation against bronchial diseases.

Keywords: Asthma, GPCR, NPSR1, drug-drug conjugates, monoclonal-antibody conjugates, drug shifting.

Graphical Abstract
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