Research Highlights
![8UTA, yjdF riboswitch from R. gauvreauii in complex with proflavine bound to Fab BL3-6 S97N 8UTA, yjdF riboswitch from R. gauvreauii in complex with proflavine bound to Fab BL3-6 S97N](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/8uta_assembly-1.jpeg?itok=THvMWlkS)
Structural basis for promiscuity in ligand recognition by yjdF riboswitch. Cell Discov. 10, 37 (2024)
![Structure of dimeric FAM111A SPD S541A Mutant, 8S9K 8S8K, Structure of dimeric FAM111A SPD S541A Mutant](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/8s9k_assembly-1.jpeg?itok=eK7ls9gF)
Dimerization-dependent serine protease activity of FAM111A prevents replication fork stalling at topoisomerase 1 cleavage complexes. Nat Commun. 15, 2064 (2024)
![8TD1 Structure of PYCR1 complexed with 3-(6-Oxa-9-azaspiro(4.5)decane-9-carbonyl)benzoic acid](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/8td1_assembly-1.jpeg?itok=KFO-b1qg)
Novel Fragment Inhibitors of PYCR1 from Docking-Guided X-ray Crystallography. J Chem Inf Model. 64, 1704-1718 (2024)
![8T7F Structure of the S1 variant of Fab F1](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/8t7f_assembly-1.jpeg?itok=c5MgGU2y)
Engineered Antigen-Binding Fragments for Enhanced Crystallization of Antibody:Antigen Complexes. Protein Sci. 10.1002/pro.4824 (2023)
![7LV2 GSQASS segment from the Nucleoprotein of SARS-CoV-2, residues 179-184](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7lv2_model-1.jpeg?itok=sO61-VvS)
Low complexity domains of the nucleocapsid protein of SARS-CoV-2 form amyloid fibrils. Nat Commun. 14, 2379 (2023)
![8GIA Crystal structure of SARS-CoV-2 (Covid-19) Nsp3 macrodomain in complex with TFMU-ADPr](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/8gia_assembly-1.jpeg?itok=uzF3cBG6)
A Fluorescence Polarization Assay for Macrodomains Facilitates the Identification of Potent Inhibitors of the SARS-CoV-2 Macrodomain. ACS Chem Biol. 18, 1200-1207 (2023)
![8DP3 Crystal structure of coxsackievirus B3 cloverleaf RNA replication element](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/8dp3_assembly-1.jpeg?itok=KKlcTQ2J)
Crystal structure of a highly conserved enteroviral 5' cloverleaf RNA replication element. Nat Commun. 14, 1955 (2023)
![Crystal structure of SARS CoV-2 Spike Receptor Binding Domain in complex with shark neutralizing VNARs ShAb01 and ShAb02 7S83](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7s83_assembly-1_0.jpeg?itok=wgGRBms4)
Shark nanobodies with potent SARS-CoV-2 neutralizing activity and broad sarbecovirus reactivity. Nat Commun. 14, 580 (2023)
![8EKH I-2 Y35N H35N (unbound) Fab from CH65-CH67 lineage](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/8ekh_assembly-1.jpeg?itok=8lsQtvi6)
Hierarchical sequence-affinity landscapes shape the evolution of breadth in an anti-influenza receptor binding site antibody. Elife. 10.7554/eLife.83628 (2023)
A unifying Bayesian framework for merging X-ray diffraction data. Nat Commun. 13, 7764 (2022)
![Crystal structure of the Thermus thermophilus 70S ribosome in complex with mRNA, aminoacylated A-site Phe-NH-tRNAphe, peptidyl P-site fMSEAC-NH-tRNAmet, and deacylated E-site tRNAphe at 2.40A resolution Crystal structure of the Thermus thermophilus 70S ribosome in complex with mRNA, aminoacylated A-site Phe-NH-tRNAphe, peptidyl P-site fMSEAC-NH-tRNAmet, and deacylated E-site tRNAphe at 2.40A resolution](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/8cvj_assembly-1.jpeg?itok=5wLCL-89)
Insights into the ribosome function from the structures of non-arrested ribosome-nascent chain complexes. Nat Chem. 10.1038/s41557-022-01073-1 (2022)
![7MEQ Crystal structure of human TMPRSS2 in complex with Nafamostat](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7meq_assembly-1.jpeg?itok=n4KCaRtS)
Structure and activity of human TMPRSS2 protease implicated in SARS-CoV-2 activation. Nat Chem Biol. 10.1038/s41589-022-01059-7 (2022)
![Crystal structure of potent neutralizing antibody 10-40 in complex with Sarbecovirus bat SHC014 receptor-binding domain 7TTM](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7ttm_assembly-1.jpeg?itok=QkhfjYDj)
An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses. Sci Transl Med. 10.1126/scitranslmed.abn6859 (2022)
![7TIU Crystal structure of SARS-CoV-2 3CL in complex with inhibitor EB46](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7tiu_assembly-1.jpeg?itok=jVAKh0Ss)
Development of optimized drug-like small molecule inhibitors of the SARS-CoV-2 3CL protease for treatment of COVID-19. Nat Commun. 13, 1891 (2022)
![7TGR Structure of SARS-CoV-2 main protease in complex with GC376](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7tgr_assembly-1.jpeg?itok=JdCT1jd4)
Gain-of-Signal Assays for Probing Inhibition of SARS-CoV-2 M/3CL in Living Cells. mBio. 10.1128/mbio.00784-22 (2022)
![7TE1 SARS-CoV-2 Receptor Binding Domain in Complex with Ab17](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7te1_assembly-1.jpeg?itok=SWgKKZhI)
Rationally designed immunogens enable immune focusing following SARS-CoV-2 spike imprinting. Cell Rep. 38, 110561 (2022)
![7F7E, SARS-CoV-2 S protein RBD in complex with A5-10 Fab SARS-CoV-2 S protein RBD in complex with A5-10 Fab](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7f7e_assembly-1.jpeg?itok=1CkhkFxl)
Etesevimab in combination with JS026 neutralizing SARS-CoV-2 and its variants. Emerg Microbes Infect. 11, 548-551 (2022)
![Crystal structure of the SARS-CoV-2 ExoN-nsp10 complex 7MC5](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7mc5_assembly-1.jpeg?itok=ZTvBMs1i)
Structure and dynamics of SARS-CoV-2 proofreading exoribonuclease ExoN. Proc Natl Acad Sci U S A. 10.1073/pnas.2106379119 (2022)
![7MLG Crystal Structure of SARS-CoV-2 Main Protease (3CLpro/Mpro) Covalently Bound to Compound C63](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7mlg_assembly-1.jpeg?itok=d9zJpEF8)
Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CL covalent inhibitors.. Eur J Med Chem. 229, 114046 (2022)
![7MKY SARS-CoV-2 frameshifting pseudoknot RNA](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7mky_assembly-1.jpeg?itok=ltxOTEGI)
Crystal structure of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) frameshifting pseudoknot. RNA. 10.1261/rna.078825.121 (2022)
![7SPO Crystal structure of the SARS-CoV-2 receptor binding domain in complex with VNAR 3B4](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7spo_assembly-1.jpeg?itok=KvWI3-4k)
Mechanisms of SARS-CoV-2 neutralization by shark variable new antigen receptors elucidated through X-ray crystallography. Nat Commun. 12, 7325 (2021)
![Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing human antibody WRAIR-2057 7N4I](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7n4i_assembly-1.jpeg?itok=zf8apA3a)
Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations. Nat Immunol. 10.1038/s41590-021-01068-z (2021)
![T. thermophilus 70S ribosome in complex with IBX, mRNA, deacylated A-site tRNAPhe, aminoacylated P-site fMet-NH-tRNAiMet, and deacylated E-site tRNAPhe 7RQ8](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7rq8_assembly-1.jpeg?itok=IEkMfqCb)
A synthetic antibiotic class overcoming bacterial multidrug resistance. Nature. 10.1038/s41586-021-04045-6 (2021)
![Crystal structure of the SARS CoV-1 Papain-like protease in complex with peptide inhibitor VIR251 7LFV](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7lfv_assembly-1.jpeg?itok=xitUXeJO)
A molecular sensor determines the ubiquitin substrate specificity of SARS-CoV-2 papain-like protease. Cell Rep. 36, 109754 (2021)
![7N0I Structure of the SARS-CoV-2 N protein C-terminal domain bound to single-domain antibody E2](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7n0i_assembly-1.jpeg?itok=VEcu6OuH)
Structural Basis for SARS-CoV-2 Nucleocapsid Protein Recognition by Single-Domain Antibodies. Front Immunol. 12, 719037 (2021)
![7MGS SARS-CoV-2 main protease in complex with N-terminal autoprocessing substrate](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7mgs_assembly-1.jpeg?itok=sOLGdpuG)
Recognition of Divergent Viral Substrates by the SARS-CoV-2 Main Protease. ACS Infect Dis. 10.1021/acsinfecdis.1c00237 (2021)
![7N44 Crystal structure of the SARS-CoV-2 (2019-NCoV) main protease in complex with 5-(3-{3-chloro-5-[(5-methyl-1,3-thiazol-4-yl)methoxy]phenyl}-2-oxo-2H-[1,3'-bipyridin]-5-yl)pyrimidine-2,4(1H,3H)-dione (compound 13)](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7n44_assembly-1.jpeg?itok=V_Uskmkp)
Optimization of Triarylpyridinone Inhibitors of the Main Protease of SARS-CoV-2 to Low-Nanomolar Antiviral Potency. ACS Med Chem Lett. 12, 1325-1332 (2021)
![7KM5 Crystal structure of SARS-CoV-2 RBD complexed with Nanosota-1](https://necat.chem.cornell.edu/sites/default/files/styles/medium/public/7km5_assembly-1.jpeg?itok=zdWT_nxA)
The development of Nanosota-1 as anti-SARS-CoV-2 nanobody drug candidates. Elife. 10.7554/eLife.64815 (2021)