Xufang Deng, Ph.D. is an Assistant Professor of Virology in the Department of Physiological Sciences at the College of Veterinary Medicine, Oklahoma State University. Dr. Deng's laboratory focuses on uncovering the fundamental biology of viral infections to guide the development of preventive and therapeutic strategies. His lab leads several active research programs, including studies on coronavirus (CoV) - host interaction, viral evasion of host immunity, vaccine and antiviral development, and SARS-CoV-2 evolution and risk assessment in wildlife. Dr. Deng’s team employs a range of classic virology, immunology, and molecular and cell biology techniques, as well as advanced tools such as reverse genetics, CRISPR-Cas, pseudotyped lentivirus, primary cell differentiation, and transgenic mouse models. Our work spans in vitro and in vivo experiments conducted in BSL2 and BSL3 facilities.

Research Interests:

(1) Virus-host interaction and viral antagonism of host immunity.

CoVs are the largest known RNA viruses that encode over 20 proteins necessary for viral replication and antagonizing the host antiviral immune system. Understanding the details of virus-host interaction and identifying key players involving these processes are crucial for discovering viral "achilles heel" as antiviral targets. We previously reported that the CoV non-structural protein 15 (Nsp15), a viral endoribonuclease, is an essential factor in antagonizing the host dsRNA antiviral signaling. We currently attempt to reveal the role of Nsp15 in the pathogenesis and tissue tropism of SARS-CoV-2. 

(2) Rational design of live-attenuated vaccines against enteric porcine coronavirus diseases 

Six porcine coronaviruses (CoVs) have been discovered to date, four of which - TGEV, PEDV, PDCoV, and the recently emerged, bat-origin SADS-CoV - can cause severe enteric diseases in piglets. These CoVs pose significant threats to the pork industry, yet effective vaccines remain unavailable. Our research aims to understand the molecular pathogenesis of enteric CoVs and leverage this knowledge for rational vaccine design. Our current research focuses on decoding the hierarchical antagonism mechanisms of porcine CoVs and developing a generalizable approach to creating genetically modified live-attenuated vaccine prototypes. We primarily use reverse genetic systems, in vitro and in vivo animal models, and CRISPR-Cas9 technology to achieve these goals.

(3) Development and evaluation of CoV protease inhibitors as antivirals

All CoVs encode two essential proteases, papain-like protease, and 3C-like protease, which play crucial roles in the viral life cycle and are primary targets for direct-acting antiviral development. In collaboration with medicinal chemistry and protein structure teams at Rutgers University, we have an active research program aimed at developing and evaluating protease inhibitors as antiviral candidates against SARS-CoV-2. Using in vitro cell culture and in vivo mouse models with live viral infection under BSL-3/ABSL-3 conditions, we have identified small-molecule compounds with potent oral efficacy against SARS-CoV-2 infection. Additionally, we are investigating viral drug resistance to clinically approved drugs and preclinical candidates to pinpoint mutational hotspots, guiding the design of next-generation antivirals.

(4) Transmission and evolution of SARS-CoV-2 in wild and zoo animals

SARS-CoV-2 is capable of infecting various animal species and continues to evolve and adapt to new hosts. This raises a significant risk of novel animal-derived SARS-CoV-2 variants spilling back into the human population, potentially leading to outbreaks due to limited human immunity against these new variants. This collaborative project, in partnership with the diagnostic team at UIUC, aims to monitor the evolution of SARS-CoV-2 in wild and zoo animals and assess the risk of these variants spilling over to humans. We use ARTIC-Amplicon sequencing to identify emerging variants and a spike-pseudotyped lentiviral system as a surrogate to evaluate the infectivity and immune escape potential of these variants.