The research team of Tsinghua University, Institute of Microbiological Epidemiology of the Academy of Military Medical Sciences, Shenzhen CDC of Guangdong Province and University of Connecticut University of The United States conducted functional screening of the pigmented protein with antiviral activity and identified two broad-spectrum antiviral bacterial proteins with lipothane activity. Both bacterial proteins have broad-spectrum antiviral activity for denge virus (DENV), Zika virus (ZIKV), Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV) and herpes simplex virus (HSV).
On May 22, local time, the research team published the study online on the preprinted website bioRxiv, entitled “Broad-spectrum virucidal activity y secret-bruned lipases, SARS-CoV-2 and otherd viruses”. The paper is written by Professor Cheng Gong of Tsinghua University School of Medicine.
The paper points out that the virus is the main pathogen of acute and chronic serious human diseases, which imposes a huge burden on global public health and economy. According to statistics, billions of reports of viral infections are reported each year, and millions of patients have severe clinical symptoms or even death. However, for most viruses, there is a lack of effective prevention and treatment measures, especially broad-spectrum antiviral drugs.
A previous study found that a soil bacteria called the Csp_P of the Aedes aegypti mosquito, which was captured in the wild, showed strong antiviral activity against the dengue virus. For the study, the team first discovered a pigmentbacterium in the intestines of the Aedes aegypti mosquito, which is raised in their insect facilities, and named the bacteria Csp_BJ. The researchers sequenced the Csp_BJ bacterial genome and uploaded the data to the NCBI database (NCBI classification number: 2735795).
They then screened and identified two progestos-active antiviral effect factors CbAE-1 and CbAE-2 from the Csp_BJ of pigmente bacteria. Both CbAEs exhibit strong antiviral activity against a variety of envelope viruses, including DENV, ZIKV, SARS-CoV-2, HIV-1 and HSV-1.
It is important to note that neither CbAEs have an effect on influenza A viruses (IAVs).
Toxicity assessments showed that CbAE-2 was much safer than CbAE-1 in both human cells and mice.
In fact, there is growing evidence that certain lipoenzymes have strong antiviral activity. A 2010 study found 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 secretive phospholipase A2 (PLA2) isolated from the snake venom of indian cobras has strong antiviral activity in HCV, DENV and the epidemic of encephalitis B (JEV). However, the protein did not show significant antiviral activity in Sindis virus (SINV), IAV, MERS or HSV-1.
The team analyzed that CbAEs may activate the virus through their lipoenzyme activity, which can also damage cell membranes. They also pointed out that CbAEs’ specificity and affinity to the virus envelope still need to be improved, thereby further reducing its cytotoxicity and improving antiviral effects.
The team noted that SARS-CoV-2 surface protrusion protein (S protein) has a high affinity for human ACE2, so an attempt could be made to engineer CbAEs using fusion ACE2 to greatly enhance its affinity and specificity to the virus envelope. They suggest that an ACE2-CbAE structure may improve the effectiveness of blocking SARS-CoV-2 infection.
The team concluded by stressing that broad-spectrum antiviral drugs may be critical to preventing the widespread spread of newly occurring viral diseases in a timely manner, and that CbAE-2′ widespread antiviral effects and low toxicity to hosts may be a potential option. “Our research provides a way to develop broad-spectrum antiviral drugs that reduce the clinical burden of emerging virus-induced diseases. “