The research team of Tsinghua University, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Shenzhen Center for Disease Control, Guangdong University of Medicine, University of Connecticut School of Medicine conducted functional screening of secreted proteins of Pseudomonas sp. A broad-spectrum antiviral bacterial protein with lipase activity. These two bacterial proteins are effective against dengue virus (DENV), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV) and herpes simplex virus (HSV) , Have broad-spectrum antiviral activity.
On May 22 local time, the research team published the above study online on the preprint website bioRxiv, entitled “Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses “. The corresponding author of the thesis is Professor Cheng Gong of Tsinghua University School of Medicine.
The paper points out that viruses are the main cause of acute and chronic serious human diseases, causing huge public health and economic problems worldwide burden. According to statistics, billions of virus infections are reported every year, and millions of patients have severe clinical symptoms or even death. However, for most viruses, there is currently no effective prevention and treatment measures, especially the lack of broad-spectrum antiviral drugs.
A previous study found that a soil bacterium named Pigment Bacillus Csp_P identified from the midgut of Aedes aegypti mosquitoes caught in the wild showed Leather virus has strong antiviral activity. In this study, the research team first discovered a pigment bacilli from the intestinal tract of Aedes aegypti mosquitoes raised in their insect facility, and named the bacterium Csp_BJ. The researchers sequenced the Csp_BJ bacterial genome and uploaded the data to the NCBI database (NCBI classification number: 2735795).
Subsequently, they screened and identified two antiviral effectors CbAE with lipase activity from the pigment bacterium Csp_BJ -1 and CbAE-2. Both CbAEs showed strong antiviral activity against a variety of enveloped viruses including DENV, ZIKV, SARS-CoV-2, HIV-1 and HSV-1.
It is worth noting that both CbAEs have no effect on influenza A virus (IAV).
The toxicity assessment shows that CbAE-2 is much safer than CbAE-1 for both human cells and mice.
In fact, there is increasing evidence that certain lipases have strong antiviral activity. A 2010 study pointed out that in human liver cancer cells (Huh7.5), lipoprotein lipase or liver triglyceride lipase can affect hepatitis C virus (HCV) infection by degrading virus-related lipoproteins.
A 2017 study also found that a secreted phospholipase A2 (PLA2), isolated from the snake venom of the Indian cobra, had an effect on HCV, DENV and epidemic Japanese encephalitis (JEV) has strong antiviral activity. However, this protein showed no significant antiviral activity against Sindv virus (SINV), IAV, MERS or HSV-1.
The research team analyzed that CbAEs may inactivate viruses through their lipase activity and also damage cell membranes. They also pointed out that the specificity and affinity of CbAEs for the viral envelope needs to be improved, thereby further reducing their cytotoxicity and improving the antiviral effect.
The research team mentioned that the spike protein (S protein) on the surface of SARS-CoV-2 has high affinity binding to human ACE2, so you can try to use fusion ACE2 to CbAEs Engineering design greatly enhances its affinity and specificity for the viral envelope. They proposed: An ACE2-CbAE structureMay improve the efficacy of blocking SARS-CoV-2 infection.
The research team finally emphasized that broad-spectrum antiviral drugs may be crucial to prevent the widespread spread of emerging viral diseases in a timely manner, and CbAE-2 has broad resistance Viral effects and low toxicity to the host may be a potential option. “Our research provides a way to develop broad-spectrum antiviral drugs and reduce the clinical burden caused by diseases caused by emerging viruses.”