AUTHOR=Chen Xinyue , Zhou Bo , Jiang Xinyi , Zhong Huayu , You Aijing , Zou Taiyan , Zhou Chengcheng , Liu Xiaoxiao , Zhang Yonghong 

TITLE=Drug repurposing to tackle parainfluenza 3 based on multi-similarities and network proximity analysis

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1428925

DOI=10.3389/fphar.2024.1428925

ISSN=1663-9812

ABSTRACT=<p>Given that there is currently no clinically approved drug or vaccine for parainfluenza 3 (PIV3), we applied a drug repurposing method based on disease similarity and chemical similarity to screen 2,585 clinically approved chemical drugs using PIV3 potential drugs BCX-2798 and zanamivir as our controls. Twelve candidate drugs were obtained after being screened with good disease similarity and chemical similarity (<italic>S</italic> &gt; 0.50, <italic>T</italic> &gt; 0.56). When docking them with the PIV3 target protein, hemagglutinin-neuraminidase (HN), only oseltamivir was docked with a better score than BCX-2798, which indicates that oseltamivir has an inhibitory effect on PIV3. After the distance (<inline-formula id="inf1"><mml:math id="m1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msub><mml:mi>Z</mml:mi><mml:mrow><mml:mi>d</mml:mi><mml:mi>c</mml:mi></mml:mrow></mml:msub></mml:mrow></mml:math></inline-formula>) between the drug target of 14 drugs and the PIV3 disease target was measured by the network proximity method based on the PIV3 disease module, it was found that the <inline-formula id="inf2"><mml:math id="m2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msub><mml:mi>Z</mml:mi><mml:mrow><mml:mi>d</mml:mi><mml:mi>c</mml:mi></mml:mrow></mml:msub></mml:mrow></mml:math></inline-formula> values of amikacin, oseltamivir, ribavirin, and streptomycin were less than those of the control. Thus, oseltamivir is the best potential drug because it met all the above screening requirements. Additionally, to explore whether oseltamivir binds to HN stably, molecular dynamics simulation of the binding of oseltamivir to HN was carried out, and the results showed that the <italic>RMSD</italic> value of the complex tended to be stable within 100 ns, and the binding free energy of the complex was low (−10.60 kcal/mol). It was proved that oseltamivir screened by our drug repurposing method had the potential feasibility of treating PIV3.</p>