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

Author:

Alfaleh Mohamed A1234ORCID,Alsulaiman Reem M34,Almahboub Sarah A34,Nezamuldeen Leena34,Zawawi Ayat3456,Aljehani Najwa D34,Yasir Muhammad34,Abdulal Rwaa H34,Alkhaldi Rami1234,Helal Assala3472,Alamri Sawsan S34,Malki Jana34,Alhabbab Rowa Y3456,Abujamel Turki S3456,Alhakamy Nabil A12,Alnami Aisha3472,Algaissi Abdullah3489,Hassanain Mazen1011,Hashem Anwar M341213

Affiliation:

1. Department of Pharmaceutics , Faculty of Pharmacy, , Jeddah 21859 , Saudi Arabia

2. King Abdulaziz University , Faculty of Pharmacy, , Jeddah 21859 , Saudi Arabia

3. Vaccines and Immunotherapy Unit , King Fahd Medical Research Center, , Jeddah 21859 , Saudi Arabia

4. King Abdulaziz University , King Fahd Medical Research Center, , Jeddah 21859 , Saudi Arabia

5. Department of Medical Laboratory Sciences , Faculty of Applied Medical Sciences, , Jeddah 21859 , Saudi Arabia

6. King Abdulaziz University , Faculty of Applied Medical Sciences, , Jeddah 21859 , Saudi Arabia

7. Department of Pharmacology and Toxicology , Faculty of Pharmacy, , Jeddah 21859 , Saudi Arabia

8. Department of Medical Laboratories Technology , College of Applied Medical Sciences, , Jazan , Saudi Arabia

9. Jazan University , College of Applied Medical Sciences, , Jazan , Saudi Arabia

10. Department of Surgery , Faculty of Medicine, , Riyadh 11451 , Saudi Arabia

11. King Saud University , Faculty of Medicine, , Riyadh 11451 , Saudi Arabia

12. Department of Medical Microbiology and Parasitology , Faculty of Medicine, , Jeddah 21859 , Saudi Arabia

13. King Abdulaziz University , Faculty of Medicine, , Jeddah 21859 , Saudi Arabia

Abstract

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.

Funder

Jameel Fund for Infectious Disease Research and Innovation in Saudi Arabia

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

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