ACE2-Fc and DPP4-Fc decoy receptors against SARS-CoV-2 and MERS-CoV variants: a quick therapeutic option for current and future coronaviruses outbreaks

Mohamed A Alfaleh; Reem M Alsulaiman; Sarah A Almahboub; Leena Nezamuldeen; Ayat Zawawi; Najwa D Aljehani; Muhammad Yasir; Rwaa H Abdulal; Rami Alkhaldi; Assala Helal; Sawsan S Alamri; Jana Malki; Rowa Y Alhabbab; Turki S Abujamel; Nabil A Alhakamy; Aisha Alnami; Abdullah Algaissi; Mazen Hassanain; Anwar M Hashem

doi:10.1093/abt/tbad030

ACE2-Fc and DPP4-Fc decoy receptors against SARS-CoV-2 and MERS-CoV variants: a quick therapeutic option for current and future coronaviruses outbreaks

Antib Ther. 2023 Dec 12;7(1):53-66. doi: 10.1093/abt/tbad030. eCollection 2024 Jan.

Authors

Mohamed A Alfaleh^{1

2}, Reem M Alsulaiman², Sarah A Almahboub², Leena Nezamuldeen², Ayat Zawawi^{2

3}, Najwa D Aljehani², Muhammad Yasir², Rwaa H Abdulal², Rami Alkhaldi^{1

2}, Assala Helal^{2

4}, Sawsan S Alamri², Jana Malki², Rowa Y Alhabbab^{2

3}, Turki S Abujamel^{2

3}, Nabil A Alhakamy¹, Aisha Alnami^{2

4}, Abdullah Algaissi^{2

5}, Mazen Hassanain⁶, Anwar M Hashem^{2

7}

Affiliations

¹ Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21859, Saudi Arabia.
² Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21859, Saudi Arabia.
³ Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21859, Saudi Arabia.
⁴ Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21859, Saudi Arabia.
⁵ Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia.
⁶ Department of Surgery, Faculty of Medicine, King Saud University, Riyadh 11451, Saudi Arabia.
⁷ Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21859, Saudi Arabia.

Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the Middle East respiratory syndrome coronavirus (MERS-CoV) are highly pathogenic human coronaviruses (CoVs). Anti-CoVs mAbs and vaccines may be effective, but the emergence of neutralization escape variants is inevitable. Angiotensin-converting enzyme 2 and dipeptidyl peptidase 4 enzyme are the getaway receptors for SARS-CoV-2 and MERS-CoV, respectively. Thus, we reformatted these receptors as Fc-fusion decoy receptors. Then, we tested them in parallel with anti-SARS-CoV (ab1-IgG) and anti-MERS-CoV (M336-IgG) mAbs against several variants using pseudovirus neutralization assay. The generated Fc-based decoy receptors exhibited a strong inhibitory effect against all pseudotyped CoVs. Results showed that although mAbs can be effective antiviral drugs, they might rapidly lose their efficacy against highly mutated viruses. We suggest that receptor traps can be engineered as Fc-fusion proteins for highly mutating viruses with known entry receptors, for a faster and effective therapeutic response even against virus harboring antibodies escape mutations.

Keywords: ACE2; DPP4; Fc-fusion proteins; MERS-CoV; SARS-CoV-2; decoy receptors; immunoadhesins; receptor traps.