Extracellular disintegration of viral proteins as an innovative strategy for developing broad-spectrum antivirals against coronavirus

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed millions of lives worldwide, not to mention innumerable losses in the global economy and disruptions in social relationships. Unfortunately, state-of-the-art treatments still lag behind the fast emergence of new variants of concern. The key to resolve this issue is to develop broad-spectrum antivirals with innovative antiviral mechanisms in which coronaviruses are deactivated regardless of their variant development. Herein, we report a new antiviral strategy involving extracellular disintegration of viral proteins that are indispensable for viral infection with hyperanion-grafted enediyne molecules. The sulfate groups ensure low cellular permeability and rather low cytotoxicity of the molecules, while the core enediyne generates reactive radical species and causes significant damage to the spike (S) protein of coronavirus. The enediyne compounds exhibit antiviral activity at micromolar to nanomolar concentrations, and the selectivity index of up to 20,000 against four kinds of human coronaviruses, including the SARS-CoV-2 omicron variant, suggesting the high potential of this new strategy in combating the COVID-19 pandemic.

Screening of Botanical Drugs against SARS-CoV-2 Entry

An escalating pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is impacting global health. Specific treatment options for diseases caused by SARS-CoV-2 are largely lacking. Herein, we used a pseudotype virus (pv) bearing the SARS-CoV-2 S glycoprotein to screen a botanical drug library to identify an agent against SARS-CoV-2 entry. All the four hits, including angeloylgomisin O, schisandrin B, procyanidin, and oleanonic acid, were identified for effective inhibition of SARS-CoV-2 S pv entry in the micromolar range. A mechanistic study revealed that these four agents inhibit SARS-CoV-2 S pv entry by blocking S-mediated membrane fusion. Furthermore, angeloylgomisin O, schisandrin B, and oleanonic acid inhibited authentic SARS-CoV-2 with a high selective index (SI). We also showed that all the four hits could also inhibit the entry of pv of Middle East respiratory syndrome coronavirus (MERS-CoV) and newly emerged SARS-CoV-2 variants (D614G, K417N/E484K/N501Y/D614G). In drug combination studies performed in cellular antiviral assays, angeloylgomisin O and schisandrin B displayed synergistic effects in combination with remdesivir. These results indicated that angeloylgomisin O, schisandrin B, procyanidin, and oleanonic acid can inhibit SARS-CoV-2 and that they are potential therapeutic agents for COVID-19.

Comparative analysis of the intestinal microbial flora diversity of adult and young African lions / 中国兽医学报

In this study,the intestinal microbial flora diversity of adult and young African lions in the same breeding environment was detected by PCR-DGGE technique.Total bacterial DNA was extracted and 16S rDNA V3 region was amplified,then conducting PCR-DGGE.Subsequently,the specific bands of DGGE were cloned and sequenced.The bacterial species were identified by comparing the sequence through BLAST.The results indicated that the intestinal microbial flora of adult African lions includes Clostridium,Lachnospiraceae bacterium,Anaerovorax,Lactococcus,Peptostreptococcus and Blautia.While the intestinal microbial flora of young African lions is lesser,most bacteria are common to adult and young lions,such as Bacteroidetes bacterium and rumen bacterium.The UPGMA clustering analysis of the DGGE fingerprint showed the similarities of the bacteria structures between adult and young African lions were only 34％.These results revealed that the intestinal microbial flora has significant difference in different stages of African lions.This study lays a foundation for the development of microecological agents in different growth stages of wild animals.

Imaging diagnosis of intra-osseous ganglia surrounding the ankle joint / 实用放射学杂志

Objective To investigate the imaging features of intra-osseous ganglia surrounding the ankle joints and their diagnostic value.Methods Imaging features of 40 cases of intra-osseous ganglia proved by the pathology from 1 982 to 2012 were analyzed ret-rospectively.33 cases underwent radiography,26 cases underwent computed tomography (CT)and 13 cases underwent magnetic resonance imaging (MRI).Results Intra-osseous ganglia were detected at talus in 23 cases,distal tibia in 1 5 cases (8 cases in pos-terior melleolus,6 cases in medial melloulus and 1 case in anterior part of distal tibia),and lateral malleolus in 1 case.Multiple in-tra-osseous ganglia was detected in 1 case,which located in both talus and posterior malleolus.29 cases were oval,monolocular os-teolytic lesions.1 1 cases were multilocular lesions with separation.All cases were observed with slightly sclerous edge.Articular surface disruptions were observed in 1 5 cases,and lesions were connected with the joint space.① Oval cystic translucent areas with sharp and sclerous edge adjacent to the ankle joint were observed in 34 lesions of 33 cases on radiograph.Cracks were noted on the articular surface of 12 lesions.② Round translucent areas with sharp and sclerous edge were observed in 26 isolated lesions on CT images.Cracks were noted on the articular surface of 14 lesions.③ 14 lesions of 13 cases showed low to moderate signal on T1 WI and high signal on T2 WI.Cracks were observed in 4 lesions adjacent to the ankle joint,and soft tissue swelling was noted in 6 le-sions.Conclusion Intra-osseous ganglia can be diagnosed accurately based on the typical imaging features and special locations.