Dr. Fang Li's Eleven Most Important Publications with Annotations (as of 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: Field-defining structural biology of coronavirus entry

Annotation: This study reported the first structure of a coronavirus spike receptor-binding domain (RBD) in complex with its cellular receptor, revealing in molecular detail how the SARS-CoV-1 spike engages human ACE2. By defining the receptor-binding interface and key determinants of host recognition, the work provided a mechanistic framework for understanding coronavirus entry, host adaptation, and cross-species transmission, including how receptor-binding mutations can facilitate viral adaptation from animals to humans. Because the RBD is a major target of neutralizing antibodies and vaccines, this structure also laid a foundation for structure-guided antibody and vaccine development. More broadly, the study became a foundational reference in coronavirus structural biology, shaping subsequent research on emerging coronaviruses and pandemic preparedness.

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: Structural framework guiding global SARS-CoV-2 research

Annotation: This study provided one of the first structures of the SARS-CoV-2 RBD in complex with human ACE2, defining the structural basis for SARS-CoV-2 receptor recognition and revealing molecular features that distinguish its receptor binding from SARS-CoV-1. It showed how a more compact ACE2-binding ridge and specific residue changes strengthen interactions with human ACE2, explaining the higher ACE2-binding affinity of the SARS-CoV-2 RBD relative to the SARS-CoV-1 RBD. The study also demonstrated that RaTG13, a closely related bat coronavirus, can use human ACE2, providing insight into potential animal-to-human transmission of SARS-CoV-2. By defining the receptor-binding interface at the outset of the COVID-19 pandemic, the study provided a critical structural framework for understanding viral entry and for developing countermeasures targeting viral entry. It became a foundational reference for subsequent research on SARS-CoV-2 entry, evolution, and antiviral strategies.

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: Mechanistic framework guiding global SARS-CoV-2 research

Annotation: This study provided the first integrated mechanistic framework for SARS-CoV-2 cell entry, identifying three key molecular features underlying this process: high-affinity ACE2 binding by the RBD, reduced RBD exposure in the spike trimer, and furin pre-activation of the spike. High receptor-binding affinity and furin pre-activation help maintain efficient cell entry, while reduced RBD exposure functions as a conformational mechanism that promotes immune evasion. Together, these molecular features allow SARS-CoV-2 to balance efficient cell entry with immune evasion and potentially contribute to its global spread. By integrating receptor binding, RBD accessibility, and protease activation, the study established a functional model linking spike structure to SARS-CoV-2 infectivity, immune evasion, and transmission. It became a foundational reference for subsequent research on viral entry, immune evasion, vaccines, and antiviral strategies during the COVID-19 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: Early predictive roadmap guiding global SARS-CoV-2 research

Annotation: This study applied a decade of structural knowledge 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 likely to shape human receptor recognition and transmission, and anticipated broad recognition of ACE2 across multiple mammalian species, with poor recognition of mouse and rat ACE2. These predictions were subsequently borne out during the pandemic, providing an early roadmap for research on viral entry, host range, zoonotic risk, and animal models. More broadly, the study demonstrated the power of structure-based predictive frameworks for responding rapidly to emerging viruses and shaped early SARS-CoV-2 research during the COVID-19 pandemic.

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 understanding coronavirus entry

Annotation: This review synthesized structural, functional, and evolutionary principles governing coronavirus spike proteins, including receptor recognition, proteolytic activation, membrane fusion, host range, and immune recognition. It explained how spike proteins coordinate receptor binding, proteolytic activation, and conformational changes to mediate viral entry, and examined how these functions evolved across coronaviruses. By integrating these diverse findings into a unified framework, the review established a conceptual foundation for understanding coronavirus entry, host adaptation, and spike evolution. Published four years before the COVID-19 pandemic, it became an essential reference for interpreting SARS-CoV-2 spike biology and for guiding vaccine and therapeutic research.

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: Structure-guided rational vaccine design

Annotation: This study used the MERS-CoV RBD as a model to investigate how epitope immunogenicity could be rationally manipulated to improve subunit vaccines. It introduced the neutralizing immunogenicity index (NII) to assess how individual epitopes contribute to neutralizing immune responses and showed that immunodominant non-neutralizing epitopes can divert immune responses away from neutralizing epitopes. Selective masking of an immunodominant non-neutralizing epitope with a glycan probe redirected immune responses toward neutralizing epitopes, enhanced neutralizing immune responses, and improved protection against lethal MERS-CoV challenge in transgenic mice. The work demonstrated how structural insights could be translated into immunogen engineering and provided proof of principle for structure-guided coronavirus 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: Rapidly adaptable nanobody antivirals

Annotation: This study introduced a 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, the approach generated nanobody variants that regained potent activity against emerging SARS-CoV-2 variants while retaining activity against earlier variants. The optimized nanobody neutralized XBB.1.5 in vitro and reduced viral replication in a mouse model. Importantly, the adaptation process could be completed in less than two weeks, providing a proof of principle for an “update rather than rediscover” strategy for rapidly re-engineering existing antiviral nanobodies 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: Novel small-molecule antivirals targeting Ebola virus entry

Annotation: This study identified MWAC-3634, a highly potent small-molecule inhibitor of Ebola virus entry, through screening of approximately 4.73 billion compounds. Structural studies revealed an unusual mechanism in which the compound stabilizes the Ebola virus glycoprotein, preventing the conformational changes required for entry, in contrast to previously described small-molecule inhibitors that destabilize the glycoprotein. MWAC-3634 inhibited authentic Ebola virus with an IC₅₀ of 0.65 nM, more than 100-fold more potent than previously reported small-molecule Ebola virus entry inhibitors, and showed favorable pharmacokinetics and substantially improved survival following oral treatment in a lethal-challenge mouse model. The study established glycoprotein stabilization as a distinct strategy for blocking Ebola virus entry and provided 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: Linking filovirus structure to viral entry efficiency and disease biology

Annotation: This study determined the first structures of Marburgvirus glycoprotein alone and in complex with its intracellular receptor NPC1, defining key mechanisms of receptor recognition and viral entry. Using a novel two-step normalization strategy that enabled direct comparison of entry efficiency across filoviruses, it showed that Marburgvirus glycoprotein mediates entry far more efficiently than Ebola virus glycoprotein. The study identified structural features that may explain this enhanced efficiency, including glycan-cap dynamics, high-affinity NPC1 engagement, and receptor-induced conformational changes. By linking glycoprotein architecture to viral entry efficiency, the study established a mechanistic framework for understanding how structural differences among filoviruses can shape viral entry and potentially contribute to differences in disease biology. The work also provided a structural framework 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: Structural biology of a cancer marker and therapeutic target

Annotation: This study determined the first structures of mammalian aminopeptidase N (APN/CD13) and its complexes with substrates and inhibitors, revealing the structural basis for its diverse roles in peptide metabolism, cell motility and adhesion, and coronavirus entry. The structures defined the catalytic mechanism of APN and showed how its accessible active site and broad peptide-binding channel enable it to process diverse substrates, while its exposed outer surface permits coronavirus binding without interfering with its enzymatic activity. Because APN is overexpressed in many cancers and associated with tumor angiogenesis and metastasis, the work also provided a structural framework for developing APN-targeting inhibitors and other therapeutics. More broadly, the study explained how the architecture of a single cell-surface protein enables multiple physiological and disease-related functions.

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: Mechanism of template-independent RNA synthesis

Annotation: This study determined the first structures of a CCA-adding enzyme and its complexes with ATP or CTP, revealing how the invariant CCA sequence is synthesized at the 3′ end of tRNAs without a nucleic acid template. The structures showed that the enzyme provides a precise and dynamic protein template for nucleotide selection, specifically recognizing ATP or CTP while excluding other nucleotides. They further revealed that a single active site can switch its specificity between CTP and ATP, providing key structural insight into sequential CCA synthesis. The work established fundamental principles of template-independent RNA polymerization and revealed a distinctive strategy by which proteins can direct nucleotide selection.