Rasha virus intrusion inhibitors were successfully screened

virus (LASV) belongs to the sand virus family, lactating sand virus genus, can cause the intense infectious disease Lassa fever, the fatality rate is very high, and there are no special drugs and vaccines. It has been classified as a Class A bioterrogen by the U.S. Centers for Disease Control and Prevention.
Recently, the Wuhan Institute of Virology of the Chinese Academy of Sciences / National Key Laboratory of Virology Xiao Weifu Research Group and Nanca University School of Pharmacy, Tianjin International Institute of Biopharmaceuticals joint research team successfully screened out inhibitors that can block the invasion of the Rasa virus, with a broad spectrum of antiviral activity. The findings have been published online in the international journal Proteins and Cells.
natural host of LASV is rodent polylactic rats, which can spread from person to person mainly through contact with animal excreta or aerosols containing the virus. LASV is mainly prevalent in West Africa, incubation period of 6 to 21 days, the main symptoms are fever, headache, sore throat, diarrhea, cough, etc. , every year 300,000 to 500,000 people infected, in hospital patients in the fatality rate of up to 70%, survivors often accompanied by deafness and other serious sequelae.
, the Health and Safety Agency of the Republic of Guinea said 82 suspected cases of Rasa fever had been detected in the central and southern parts of the country, with one confirmed death.
, the current clinical treatment for patients infected with LASV is limited to the use of the broad-spectrum antiviral drug libavirin in the early stages of infection.
, virus invasion is often the first step in the life cycle of the virus and is one of the key targets for antiviral drug design. LASV virus cystic glycoprotein GPC is composed of residual signal peptide (SSP), GP1 (participating in the recognition of the subject), GP2 (participating in membrane fusion), and the SSP-GP2 interface composed of SSP and GP2 is the main target for entering the inhibitor.
to this end, the researchers constructed a fake virus (LASVpv) and recombinative virus (LASVrv) with blistered oral inflammatory virus (VSV) as the skeleton, cystic membrane protein as LASV GPC, LASVpv and LASVrv, which can simulate the invasion process of LASV under biosecurity secondary conditions because the cystic protein is the same as LASV. Because it carries the reported gene, it can be used in high-volume screening experiments.
, the researchers obtained 72 derivatives by optimizing the configuration relationship of THESV-specific entry inhibitor ST-161, which had been reportedly screened by SIGA. And by conducting antiviral experiments on fake and recombinant viruses on different cells, they identified four best-performing Rasa viruses entering inhibitors: compounds 21, 29, 57, 72. Among them, compound 57 also has significant inhibitory effect on other four-stage pathogens in the sand grain virus department, and is expected to become a broad-spectrum inhibitor of sand grain virus.
, experiments have shown that four compounds can significantly inhibit the entry of LASV, compared to ST-161, significantly improved antiviral effect, and has a broad spectrum of antiviral activity. Its mechanism of action is to achieve antiviral effect by acting on the interaction interface between SSP and GPS2, stabilizing the pre-GPC fusion image and inhibiting membrane fusion.
industry insiders said that the above-mentioned research results not only for the outbreak of the sand virus to provide a reserve of candidate emergency drugs, but also for anti-sand virus drug research and development provides a theoretical basis and optimization strategy. (Source: Zhang Siwei, China Science Journal)