Abstract: Although COVID-19 transmission has been reduced by the advent of vaccinations and a variety of rapid monitoring techniques, the SARS-CoV-2 virus itself has shown a remarkable ability to mutate and persist. With this long track record of immune escape, researchers are still exploring prophylactic treatments to curtail future SARS-CoV-2 variants. Specifically, much focus has been placed on the antiviral lectin Griffithsin in preventing spike protein-mediated infection via the hACE2 receptor (direct infection). However, an oft-overlooked aspect of SARS-CoV-2 infection is viral capture by attachment receptors such as DC-SIGN, which is thought to facilitate the initial stages of COVID-19 infection in the lung tissue (called trans-infection). In addition, while immune escape is dictated by mutations in the spike protein, coronaviral virions also incorporate M, N, and E structural proteins within the particle. In this paper, we explored how several structural facets of both the SARS-CoV-2 virion and the antiviral lectin Griffithsin can affect and attenuate the infectivity of SARS-CoV-2 pseudovirus. We found that Griffithsin was a better inhibitor of hACE2-mediated direct infection when the coronaviral M protein is present compared to when it is absent (possibly providing an explanation regarding why Griffithsin shows better inhibition against authentic SARS-CoV-2 as opposed to pseudotyped viruses, which generally do not contain M) and that Griffithsin was not an effective inhibitor of DC-SIGN-mediated trans-infection. Furthermore, we found that DC-SIGN appeared to mediate trans-infection exclusively via binding to the SARS-CoV-2 spike protein, with no significant effect observed when other viral proteins (M, N, and/or E) were present. These results provide etiological data that may help to direct the development of novel antiviral treatments, either by leveraging Griffithsin binding to the M protein as a novel strategy to prevent SARS-CoV-2 infection or by narrowing efforts to inhibit trans-infection to focus on DC-SIGN binding to SARS-CoV-2 spike protein.

Guan W, Zhang N, Bains A, Rodriguez AM, LiWang PJ. Sustained Delivery of Antiviral Protein Griffithsin and Adhesion to A Biological Surface by A Silk Fibroin Scaffold. Materials. 2023;16.

Abstract: The protein Griffithsin (Grft) is a lectin that tightly binds to high-mannose glycosylation sites on viral surfaces. This property allows Grft to potently inhibit many viruses, including HIV-1. The major route of HIV infection is through sexual activity, so an important tool for reducing the risk of infection would be a film that could be inserted vaginally or rectally to inhibit transmission of the virus. We have previously shown that silk fibroin can encapsulate, stabilize, and release various antiviral proteins, including Grft. However, for broad utility as a prevention method, it would be useful for an insertable film to adhere to the mucosal surface so that it remains for several days or weeks to provide longer-term protection from infection. We show here that silk fibroin can be formulated with adhesive properties using the nontoxic polymer hydroxypropyl methylcellulose (HPMC) and glycerol, and that the resulting silk scaffold can both adhere to biological surfaces and release Grft over the course of at least one week. This work advances the possible use of silk fibroin as an anti-viral insertable device to prevent infection by sexually transmitted viruses, including HIV-1.


Mortazavi1 M, Bains1 A, Afsah-Hejri L, Ehsani* R, LiWang PJ. SARS-CoV-2 pseudotyped virus persists on the surface of multiple produce but can be inactivated with gaseous ozone. CellPress. 2022.

Due to the immense societal and economic impact that the COVID-19 pandemic has caused, limiting the spread of SARS-CoV-2 is one of the most important priorities at this time. The global interconnectedness of the food industry makes it one of the biggest concerns for SARS-CoV-2 outbreaks. Although fomites are currently considered a low-risk route of transmission for SARS-CoV-2, new variants of the virus can potentially alter the transmission dynamics. In this study, we compared the survival rate of pseudotyped SARS-CoV-2 on plastic with some commonly used food samples (i.e., apple, strawberry, grapes, tomato, cucumber, lettuce, parsley, Brazil nut, almond, cashew, and hazelnut). The porosity level and the chemical composition of different food products affect the virus’s stability and infectivity. Tomato, cucumber, and apple offered a higher survival rate for the pseudotyped viruses. Next, we explored the effectiveness of ozone in deactivating the SARS-CoV-2 pseudotyped virus on the surface of tomato, cucumber, and apple. We found that the virus was effectively inactivated after being exposed to 15 ppm of ozone for one hour under ambient conditions. SEM imaging revealed that while ozone exposure altered the wax layer on the surface of produce, it did not seem to damage the cells and their biological structures. The results of our study show that ozonated air can likely provide a convenient method of effectively disinfecting bulk food shipments that may harbour the SARS-CoV-2 virus.


Stark LE, Guan W, Colvin ME, LiWang PJ. “The binding and specificity of chemokine binding proteins, through the lens of experiment and computation.” Biomedical Journal. 2021.

Chemokines are small proteins that are critical for immune function, being primarily responsible for the activation and chemotaxis of leukocytes. As such, many viruses, as well as parasitic arthropods, have evolved systems to counteract chemokine function in order to maintain virulence, such as binding chemokines, mimicking chemokines, or producing analogs of transmembrane chemokine receptors that strongly bind their targets. The focus of this review is the large group of chemokine binding proteins (CBP) with an emphasis on those produced by mammalian viruses. Because many chemokines mediate inflammation, these CBP could possibly be used pharmaceutically as anti-inflammatory agents. In this review, we summarize the structural properties of a diverse set of CBP and describe in detail the chemokine binding properties of the poxvirus-encoded CBP called vCCI (viral CC Chemokine Inhibitor). Finally, we describe the current and emerging capabilities of combining computational simulation, structural analysis, and biochemical/biophysical experimentation to understand, and possibly re-engineer, protein-protein interactions.