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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the current COVID-19 global pandemic. Vaccines and therapeutics are urgently needed for this highly transmissible virus. In this study, we screened human monoclonal antibodies (mAbs) targeting the receptor binding domain (RBD) of the SARS-CoV-2 spike protein from an antibody library constructed from peripheral blood mononuclear cells of a COVID-19 convalescent patient. A potent neutralizing antibody, termed CT-P59, was identified and found to be effective against various SARS-CoV-2 isolates including the D614G spike protein variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/SARS-CoV-2 RBD showed that CT-P59 blocks interaction regions of SARS-CoV-2 RBD for its cellular receptor, angiotensin converting enzyme 2 (ACE2). The binding orientation of CT-P59 is notably different from the previously reported neutralizing mAbs targeting SARS-CoV-2 RBD suggesting that CT-P59 can be a novel binder to SARS-CoV-2 RBD. Therapeutic effects of CT-P59 were evaluated in three animal models (ferret, hamster, and rhesus monkey), and a substantial reduction in viral titre along with alleviation of clinical symptoms was observed. These findings suggest that the human monoclonal antibody, CT-P59, is a promising therapeutic candidate for treatment of COVID-19.
Figure 1
Figure 2
Figure 3
Yes there is potential Competing Interest. Patents have been filed for CT-P59. C.K., D.K.R., J.L., J.M.S., M.K., J.I.K., P.K., J.S.B., E.Y.S., M.S.L., M.S.K., H.N., G.S.P., J.S.P., D.S., Y.A., J.N.L., K.S.K. and S.Y.L. are employees of Celltrion, Inc. This work was funded by Celltrion, Inc. and several grants listed in Acknowledgements.
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryTable14Aug2020.docx
Supplementary Table 1
- ExtendedData14Aug2020.docx
Extended Data Table 1, Table 2, Table 3, Extended Data Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5, Fig. 6, Fig. 7
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See the published version of this preprint at Nature Communications.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Article
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Nature Communications.
Version 1
Posted 10 Sep, 2020
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PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Nature Communications.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the current COVID-19 global pandemic. Vaccines and therapeutics are urgently needed for this highly transmissible virus. In this study, we screened human monoclonal antibodies (mAbs) targeting the receptor binding domain (RBD) of the SARS-CoV-2 spike protein from an antibody library constructed from peripheral blood mononuclear cells of a COVID-19 convalescent patient. A potent neutralizing antibody, termed CT-P59, was identified and found to be effective against various SARS-CoV-2 isolates including the D614G spike protein variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/SARS-CoV-2 RBD showed that CT-P59 blocks interaction regions of SARS-CoV-2 RBD for its cellular receptor, angiotensin converting enzyme 2 (ACE2). The binding orientation of CT-P59 is notably different from the previously reported neutralizing mAbs targeting SARS-CoV-2 RBD suggesting that CT-P59 can be a novel binder to SARS-CoV-2 RBD. Therapeutic effects of CT-P59 were evaluated in three animal models (ferret, hamster, and rhesus monkey), and a substantial reduction in viral titre along with alleviation of clinical symptoms was observed. These findings suggest that the human monoclonal antibody, CT-P59, is a promising therapeutic candidate for treatment of COVID-19.
Figure 1
Figure 2
Figure 3
Yes there is potential Competing Interest. Patents have been filed for CT-P59. C.K., D.K.R., J.L., J.M.S., M.K., J.I.K., P.K., J.S.B., E.Y.S., M.S.L., M.S.K., H.N., G.S.P., J.S.P., D.S., Y.A., J.N.L., K.S.K. and S.Y.L. are employees of Celltrion, Inc. This work was funded by Celltrion, Inc. and several grants listed in Acknowledgements.
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryTable14Aug2020.docx
Supplementary Table 1
- ExtendedData14Aug2020.docx
Extended Data Table 1, Table 2, Table 3, Extended Data Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5, Fig. 6, Fig. 7
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