Dr. Fang Li's Top Eleven Most Important Publications with Annotations (by September, 2026)

1. Li, F., Li, W., Farzan, M., Harrison, S.C. (2005). Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science

Impact: Defining new fields

Annotation: This study reported the first atomic structure of a coronavirus spike receptor-binding domain in complex with its receptor. It defined how the SARS-CoV-1 spike engages human ACE2 and provided a structural framework for understanding receptor recognition, host adaptation, and cross-species transmission. Follow-up work from my laboratory used this framework to identify key receptor-binding mutations associated with adaptation from palm civets to humans. Because the RBD is also a major target of neutralizing antibodies and vaccines, this structural framework subsequently informed receptor-blocking antibody and RBD-based vaccine strategies. The study laid the foundation for structural studies of coronavirus entry and cross-species transmission. Google Scholar citations: 2,645 (September 2026).

2. Shang, J., Ye, G., Shi, K., Wan, Y., Luo, C., Aihara, H., Geng, Q., Auerbach, A., Li, F. (2020). Structural basis of receptor recognition by SARS-CoV-2. Nature

Impact: Guiding global pandemic research

Annotation: This study defined the structural basis for SARS-CoV-2 recognition of human ACE2 and identified molecular features that distinguish its receptor binding from SARS-CoV-1. It showed that the SARS-CoV-2 RBD binds human ACE2 substantially more tightly and revealed structural features, including a more compact ACE2-binding ridge, that strengthen receptor interactions. The structure also identified key receptor-binding sites and mutations relevant to host adaptation and provided a blueprint for antibody therapeutics and RBD-based vaccine design. Together with our subsequent mechanistic studies, this work guided global research on SARS-CoV-2 entry, evolution, vaccines, and antibody therapeutics during the COVID-19 pandemic. Google Scholar citations: 4,610 (September 2026).

3. Shang, J., Wan, Y., Luo, C., Ye, G., Geng, Q., Auerbach, A., Li, F. (2020). Cell entry mechanisms of SARS-CoV-2. PNAS

Impact: Guiding global pandemic research

Annotation: This study identified three key structural mechanisms underlying SARS-CoV-2 cell entry: high-affinity ACE2 binding by the RBD, a more hidden RBD in the spike trimer, and furin pre-activation of the spike. The hidden RBD reduces immune exposure, while high receptor-binding affinity and furin pre-activation help maintain efficient viral entry despite reduced RBD accessibility; furin pre-activation also enhances entry into cells expressing low levels of ACE2. Together, these findings provided a mechanistic framework for understanding how SARS-CoV-2 combines immune evasion with efficient cell entry, features that likely contributed to its global spread. The study guided worldwide research on SARS-CoV-2 entry, immune evasion, vaccines, and antiviral strategies during the pandemic. Google Scholar citations: 4,056 (September 2026).

4. Wan, Y., Shang, J., Graham, R., Baric, R.S., Li, F. (2020). Receptor recognition by the novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS coronavirus. Journal of Virology

Impact: Guiding global pandemic research

Annotation: Published at the outset of the COVID-19 outbreak, this study applied structural knowledge accumulated from SARS-CoV-1 to make early molecular predictions about the newly emerged SARS-CoV-2. It predicted ACE2 receptor usage, identified key RBD residues as important mutation and transmission hotspots, predicted broad recognition of mammalian ACE2, and anticipated poor recognition of mouse and rat ACE2. These predictions were subsequently confirmed during the pandemic and guided early research on viral entry, variants, host range, zoonotic risk, and animal models. Google Scholar citations: 5,952 (September 2026); the most cited paper in the history of Journal of Virology (Crossref; as of March 2026).

5. Li, F. (2016). Structure, function and evolution of coronavirus spike proteins. Annual Review of Virology

Impact: Gateway to coronavirus entry

Annotation: This review synthesized structural, functional, and evolutionary principles governing coronavirus spike proteins, including receptor recognition, proteolytic activation, membrane fusion, host range, tissue tropism, and immune recognition. It provided a unified conceptual framework for understanding coronavirus spikes as central determinants of viral entry and as major targets for vaccines and therapeutics. Google Scholar citations: 3,711 (September 2026); the most cited paper in the history of Annual Review of Virology (Crossref; as of March 2026).

6. Du, L., Tai, W., Yang, Y., Zhao, G., Zhu, Q., Sun, S., Liu, C., Tao, X., Tseng, C., Perlman, S., Jiang, S., Zhou, Y., Li, F. (2016). Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines. Nature Communications

Impact: Vaccine research

Annotation: This study showed that epitope shielding can be used to rationally improve coronavirus subunit vaccines. By selectively masking epitopes with glycan probes, the study demonstrated that immunodominant non-neutralizing epitopes can divert immune responses. Masking a negative-immunogenicity epitope increased neutralizing antibody responses and improved protection against lethal MERS-CoV challenge in transgenic mice. The work established epitope shielding as a structure-guided strategy for vaccine design.

7. Ye, G., Bu, F., Pan, R., Mendoza, A., Yang, G., Spiller, B., Wadzinski, B.E., Du, L., Perlman, S., Liu, B., Li, F. (2024). Structure-guided in vitro evolution of nanobodies targeting new viral variants. PLOS Pathogens

Impact: Antiviral nanobodies

Annotation: This study introduced a novel structure-guided strategy for rapidly adapting antiviral nanobodies to viral escape mutations. By identifying mutations at the virus–nanobody interface and selectively randomizing nearby nanobody residues, we generated evolved nanobodies that regained activity against emerging SARS-CoV-2 variants while retaining activity against earlier strains. In the proof-of-concept study, the process could be completed in less than two weeks, demonstrating an “update, don’t rediscover” strategy for maintaining antiviral activity as viruses evolve.

8. Bu, F., Ye, G., Sharma, K.L., La Rosa, B., Palaniappan, M., Matzuk, M.M., Young, D.W., Turner-Hubbard, H., Morsheimer, K., Owen, C., Toth, K., Cameron, M., Davey, R., Chamakuri, S., Dosa, P., Li, F. (2026). A small molecule inhibits Ebola virus entry through glycoprotein stabilization. Nature Communications

Impact: Antiviral small-molecule compounds

Annotation: This study identified MWAC-3634, a highly potent small-molecule inhibitor of Ebola virus entry, through DNA-encoded screening of approximately 4.73 billion molecules. Structural studies revealed an unusual mechanism in which the compound stabilizes the Ebola virus glycoprotein, preventing the conformational changes required for viral entry. MWAC-3634 inhibited authentic Ebola virus with an IC₅₀ of 0.65 nM, was at least 100-fold more potent than previously reported small-molecule Ebola entry inhibitors, and substantially improved survival and reduced viral load following oral treatment in a preclinical model. The study establishes glycoprotein stabilization as a new strategy for blocking Ebola virus entry and provides a structural blueprint for further antiviral optimization.

9. Ye, G., Bu, F., Turner-Hubbard, H., Herbst, M., Du, L., Yang, G., Liu, B., Li, F. (2026). Structures of Marburgvirus glycoprotein and its complex with NPC1 receptor. Nature

Impact: Filovirus entry

Annotation: This study determined cryo-EM structures of Marburgvirus glycoprotein in multiple functional states, including its complex with the intracellular receptor NPC1, and defined structural mechanisms underlying receptor engagement and viral entry. The work revealed candidate mechanisms associated with the unusually efficient entry of Marburgvirus GP, including glycan-cap dynamics, high-affinity NPC1 engagement, and receptor-induced conformational changes. It established a structural and mechanistic framework for Marburgvirus entry and provides a foundation for developing filovirus entry inhibitors.

10. Chen, L., Lin, Y.-L., Peng, G., Li, F. (2012). Structural basis for multifunctional roles of mammalian aminopeptidase N. PNAS

Impact: Cancer marker

Annotation: This study determined the first atomic structures of mammalian aminopeptidase N (APN/CD13) and its complexes with substrates and inhibitors, revealing the structural basis for its diverse functions in peptide metabolism, cell motility and adhesion, and coronavirus entry. Because APN is highly expressed in many cancers and plays important roles in tumor angiogenesis and metastasis, the structures also provided a framework for developing therapeutics targeting APN-related diseases.

11. Li, F., Xiong, Y., Wang, J., Cho, H.D.D., Tomita, K., Weiner, A.M., Steitz, T.A. (2002). Crystal structures of the Bacillus stearothermophilus CCA-adding enzyme and its complexes with ATP or CTP. Cell

Impact: Template-independent RNA synthesis

Annotation: This study determined the first atomic structures of a CCA-adding enzyme and its complexes with ATP or CTP, providing a structural basis for understanding how the enzyme synthesizes the invariant CCA sequence at the 3′ end of tRNAs without using a nucleic acid template. The work revealed the enzyme’s distinctive four-domain architecture and provided fundamental insight into template-independent RNA polymerization.