Virtual screening and activity study of antiviral compounds targeting inosine 5'-monophosphate dehydrogenase

Inosine 5'-monophosphate dehydrogenase (IMPDH) is a key enzyme catalyzing the rate-limiting step of de novo nucleotide synthesis in vivo. In recent years, it has become a therapeutic target for anti-virus, antibacterial, anti-cancer, anti-parasitic and other diseases. IMPDH inhibitors have been shown to inhibit viral proliferation in host cells by depleting guanosine 5'-monophosphate (GMP), the raw material required for viral replication in host cells, with broad-spectrum antiviral properties. In order to find novel anti-coronavirus drugs, this study screened 22 potential IMPDH inhibitors from 70 000 natural small molecule libraries based on IMPDH protein structure using molecular docking and ROC calculation for virtual screening. With ribavirin as the positive control drug, Huh7 cell and H460 cell models were used to verify the anti-coronavirus HCoV-229E and HCoV-OC43 activities of 22 selected target compounds. Among them, compounds 11, 12, 15 and 16 showed inhibitory activity against coronavirus HCoV-229E. The compounds 4, 12, 13 and 15 showed inhibitory activities against coronavirus HCoVOC43. 12 and 15 showed significant inhibitory activity against both two coronaviruses, and their efficacy was similar to ribavirin at the same dose, which can be further studied as a lead compound for IMPDH inhibitors. Copyright © 2022, Chinese Pharmaceutical Association. All rights reserved.

Influence of landscape outside the window on the anxiety level of self-separation people during COVID-19

Windows are the communication medium between indoor and outdoor, but their influence and the corresponding landscape outside the window are often ignored due to the outdoor frequent activities of people. The coronavirus disease 2019 (COVID-19) has been a better choice to show the window performance, especially for the anxiety level alleviation of people isolated at home. A national survey was conducted on the anxiety of self-separation people and the window influence. The results showed that the average anxiety level was 1.54, between a little anxious and anxious, due to the COVID-19. The best satisfaction with the landscape outside the window was waterscape (2.98), followed by green plants (2.33) and buildings (0.83). During the COVID-19, the average number of overlook times increased by 1.49 times/day, which is higher 0.42 ties/day than the normal condition. The landscape types had the certain influence on the overlook frequency, the window opening times and even the anxiety level. The average anxiety levels are 1.36 and 1.68 with natural landscapes and human landscapes, respectively. Optimizing the landscapes outside the window plays an important role in alleviating the anxiety of residents and improving their mental health.