Challenges and opportunities for antiviral monoclonal antibodies as COVID-19 therapy

Carlos Cruz-Teran; Karthik Tiruthani; Morgan McSweeney; Alice Ma; Raymond Pickles; Samuel K Lai

doi:10.1016/j.addr.2020.12.004

Challenges and opportunities for antiviral monoclonal antibodies as COVID-19 therapy

Adv Drug Deliv Rev. 2021 Feb:169:100-117. doi: 10.1016/j.addr.2020.12.004. Epub 2020 Dec 9.

Authors

Carlos Cruz-Teran¹, Karthik Tiruthani¹, Morgan McSweeney², Alice Ma³, Raymond Pickles⁴, Samuel K Lai⁵

Affiliations

¹ Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
² Inhalon Biopharma, Durham, NC 27709, USA.
³ UNC/NCSU Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴ Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁵ Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Inhalon Biopharma, Durham, NC 27709, USA; UNC/NCSU Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: lai@unc.edu.

Abstract

To address the COVID-19 pandemic, there has been an unprecedented global effort to advance potent neutralizing mAbs against SARS-CoV-2 as therapeutics. However, historical efforts to advance antiviral monoclonal antibodies (mAbs) for the treatment of other respiratory infections have been met with categorical failures in the clinic. By investigating the mechanism by which SARS-CoV-2 and similar viruses spread within the lung, along with available biodistribution data for systemically injected mAb, we highlight the challenges faced by current antiviral mAbs for COVID-19. We summarize some of the leading mAbs currently in development, and present the evidence supporting inhaled delivery of antiviral mAb as an early intervention against COVID-19 that could prevent important pulmonary morbidities associated with the infection.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Angiotensin-Converting Enzyme 2 / antagonists & inhibitors
Angiotensin-Converting Enzyme 2 / metabolism
Animals
Antibodies, Monoclonal / chemistry
Antibodies, Monoclonal / metabolism
Antibodies, Monoclonal / therapeutic use*
Antiviral Agents / chemistry
Antiviral Agents / metabolism
Antiviral Agents / therapeutic use*
COVID-19 / diagnosis
COVID-19 / metabolism
COVID-19 / therapy*
COVID-19 Serotherapy
Humans
Immunization, Passive
Immunologic Factors / chemistry
Immunologic Factors / metabolism
Immunologic Factors / therapeutic use*
Protein Structure, Secondary
Protein Structure, Tertiary
SARS-CoV-2 / chemistry
SARS-CoV-2 / drug effects*
SARS-CoV-2 / metabolism
Virus Shedding / drug effects
Virus Shedding / physiology

Substances

Antibodies, Monoclonal
Antiviral Agents
Immunologic Factors
Angiotensin-Converting Enzyme 2

Abstract

Publication types

MeSH terms

Substances

Grants and funding