Structural Basis of the Main Proteases of Coronavirus Bound to Drug Candidate PF-07321332Jian Li, Cheng‐Wen Lin, Xuelan Zhou et al.|Journal of Virology|2022 The current pandemic of multiple variants has created an urgent need for effective inhibitors of SARS-CoV-2 to complement vaccine strategies. PF-07321332, developed by Pfizer, is the first orally administered coronavirus-specific main protease inhibitor approved by the FDA. We solved the crystal structures of the main protease of SARS-CoV-2, SARS-CoV, and MERS-CoV that bound to the PF-07321332, suggesting PF-07321332 is a broad-spectrum inhibitor for coronaviruses. Structures of the main protease inhibitor complexes present an opportunity to discover safer and more effective inhibitors for COVID-19.
Genetic characterization of Toxoplasma gondii from pigs from different localities in China by PCR-RFLPBACKGROUND: Toxoplasma gondii is a widely prevalent protozoan parasite that causes serious toxoplasmosis in humans and animals. The present study aimed to determine the genetic diversity of T. gondii isolates from pigs in Jiangxi, Sichuan, Guangdong Provinces and Chongqing Municipality in China using multilocous polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. METHODS: A total of 38 DNA samples were extracted from hilar lymph nodes of pigs with suspected toxoplasmosis, and were detected for the presence of T. gondii by semi-nested PCR of B1 gene. The positive DNA samples were typed at 11 genetic markers, including 10 nuclear loci, namely, SAG1, 5'-SAG2 and 3'-SAG2, alternative SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and an apicoplast locus Apico. RESULTS: Twenty-five of the 38 DNA samples were T. gondii B1 gene positive. Complete genotyping data for all loci could be obtained for 17 of the 25 samples. Two genotypes were revealed (ToxoDB PCR-RFLP genotypes #9 and #3). Sixteen samples belong to genotype #9 which is the major lineage in mainland China and one sample belongs to genotype #3 which is Type II variant. CONCLUSIONS: To our knowledge, this is the first report of genetic typing of T. gondii isolates from pigs in Jiangxi, Sichuan Province and Chongqing Municipality, and the first report of ToxoDB #3 T. gondii from pigs in China. These results have implications for the prevention and control of foodborne toxoplasmosis in humans.
Potential Inhibitors Targeting Papain-Like Protease of SARS-CoV-2: Two Birds With One StoneHaihai Jiang, Peiyao Yang, Jin Zhang|Frontiers in Chemistry|2022 Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the pathogen of the Coronavirus disease-19 (COVID-19), is still devastating the world causing significant chaos to the international community and posing a significant threat to global health. Since the first outbreak in late 2019, several lines of intervention have been developed to prevent the spread of this virus. Nowadays, some vaccines have been approved and extensively administered. However, the fact that SARS-CoV-2 rapidly mutates makes the efficacy and safety of this approach constantly under debate. Therefore, antivirals are still needed to combat the infection of SARS-CoV-2. Papain-like protease (PLpro) of SARS-CoV-2 supports viral reproduction and suppresses the innate immune response of the host, which makes PLpro an attractive pharmaceutical target. Inhibition of PLpro could not only prevent viral replication but also restore the antiviral immunity of the host, resulting in the speedy recovery of the patient. In this review, we describe structural and functional features on PLpro of SARS-CoV-2 and the latest development in searching for PLpro inhibitors. Currently available inhibitors targeting PLpro as well as their structural basis are also summarized.