tetano
Editor, Senior Moderator
Antib Ther
. 2023 Dec 12;7(1):53-66.
doi: 10.1093/abt/tbad030. eCollection 2024 Jan. 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[SUP] 1 2 [/SUP], Reem M Alsulaiman[SUP] 2 [/SUP], Sarah A Almahboub[SUP] 2 [/SUP], Leena Nezamuldeen[SUP] 2 [/SUP], Ayat Zawawi[SUP] 2 3 [/SUP], Najwa D Aljehani[SUP] 2 [/SUP], Muhammad Yasir[SUP] 2 [/SUP], Rwaa H Abdulal[SUP] 2 [/SUP], Rami Alkhaldi[SUP] 1 2 [/SUP], Assala Helal[SUP] 2 4 [/SUP], Sawsan S Alamri[SUP] 2 [/SUP], Jana Malki[SUP] 2 [/SUP], Rowa Y Alhabbab[SUP] 2 3 [/SUP], Turki S Abujamel[SUP] 2 3 [/SUP], Nabil A Alhakamy[SUP] 1 [/SUP], Aisha Alnami[SUP] 2 4 [/SUP], Abdullah Algaissi[SUP] 2 5 [/SUP], Mazen Hassanain[SUP] 6 [/SUP], Anwar M Hashem[SUP] 2 7 [/SUP]
Affiliations
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.
. 2023 Dec 12;7(1):53-66.
doi: 10.1093/abt/tbad030. eCollection 2024 Jan. 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[SUP] 1 2 [/SUP], Reem M Alsulaiman[SUP] 2 [/SUP], Sarah A Almahboub[SUP] 2 [/SUP], Leena Nezamuldeen[SUP] 2 [/SUP], Ayat Zawawi[SUP] 2 3 [/SUP], Najwa D Aljehani[SUP] 2 [/SUP], Muhammad Yasir[SUP] 2 [/SUP], Rwaa H Abdulal[SUP] 2 [/SUP], Rami Alkhaldi[SUP] 1 2 [/SUP], Assala Helal[SUP] 2 4 [/SUP], Sawsan S Alamri[SUP] 2 [/SUP], Jana Malki[SUP] 2 [/SUP], Rowa Y Alhabbab[SUP] 2 3 [/SUP], Turki S Abujamel[SUP] 2 3 [/SUP], Nabil A Alhakamy[SUP] 1 [/SUP], Aisha Alnami[SUP] 2 4 [/SUP], Abdullah Algaissi[SUP] 2 5 [/SUP], Mazen Hassanain[SUP] 6 [/SUP], Anwar M Hashem[SUP] 2 7 [/SUP]
Affiliations
- PMID: 38371953
- PMCID: PMC10873275
- DOI: 10.1093/abt/tbad030
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.