SARS-CoV-2 tetrameric RBD protein blocks viral infection and induces potent neutralizing antibody response.

The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious threats to global health and economy and calls for the development of safe treatments and effective vaccines. The receptor-binding domain in the spike protein (S^RBD) of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2 (ACE2) receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that dimeric S^RBD-Fc and tetrameric 2xS^RBD-Fc fusion proteins bind ACE2 with different affinity and block SARS-CoV-2 pseudoviral infection. Immunization of mice with S^RBD-Fc fusion proteins elicited high titer of RBD-specific antibodies with robust neutralizing activity against pseudoviral infections. As such, our study indicates that the polymeric S^RBD-Fc fusion protein can serve as a treatment agent as well as a vaccine for fighting COVID-19.

Potent Antiviral and Antimicrobial Polymers as Safe and Effective Disinfectants for the Prevention of Infections.

Disinfection using effective antimicrobials is essential in preventing the spread of infectious diseases. This COVID-19 pandemic has brought the need for effective disinfectants to greater attention due to the fast transmission of SARS-CoV-2. Current active ingredients in disinfectants are small molecules that microorganisms can develop resistance against after repeated long-term use and may penetrate the skin, causing harmful side-effects. To this end, a series of membrane-disrupting polyionenes that contain quaternary ammoniums and varying hydrophobic components is synthesized. They are effective against bacteria and fungi. They are also fast acting against clinically isolated drug resistant strains of bacteria. Formulating them with thickeners and nonionic surfactants do not affect their killing efficiency. These polyionenes are also effective in preventing infections caused by nonenveloped and enveloped viruses. Their effectiveness against mouse coronavirus (i.e., mouse hepatitis virus-MHV) depends on their hydrophobicity. The polyionenes with optimal compositions inactivates MHV completely in 30 s. More importantly, the polyionenes are effective in inhibiting SARS-CoV-2 by >99.999% within 30 s. While they are effective against the microorganisms, they do not cause damage to the skin and have a high oral lethal dose. Overall, these polyionenes are promising active ingredients for disinfection and prevention of viral and microbial infections.

Research progress on repositioning drugs and specific therapeutic drugs for SARS-CoV-2.

SARS-CoV-2 has been widely spread around the world and COVID-19 was declared a global pandemic by the WHO. Limited clinically effective antiviral drugs are available now. The development of anti-SARS-CoV-2 drugs has become an urgent work worldwide. At present, potential therapeutic targets and drugs for SARS-CoV-2 are continuously reported, and many repositioning drugs are undergoing extensive clinical research, including remdesivir and chloroquine. On the other hand, structures of many important viral target proteins and host target proteins, including that of RdRp and Mpro were constantly reported, which greatly promoted structure-based drug design. This paper summarizes the current research progress and challenges in the development of anti-SARS-CoV-2 drugs, and proposes novel short-term and long-term drug research strategies.