Biological Therapeutic Strategies against SARS-CoV-2 and COVID-19

18 years ago the SARS-CoV lead to respiratory diseases in infected people. To date there are no effective vaccines against any type of the coronavirus, which can cause pneumonia and possibly bronchitis. Nevertheless, there are several strategies that are being pursued.

COVID-19 Therapeutic Strategies

Soluble Human ACE2:
The novel coronavirus uses membrane-bound ACE2 as the receptor. The soluble form of ACE2 lacks the membrane anchor and circulates in small amounts in the blood. This soluble form may act as a competitive interceptor of SARS-CoV-2 and other coronaviruses by preventing binding of the viral particle to the surface-bound, full-length ACE2.

ACE2 fused to the Fc portion of immunoglobulin has been reported to neutralize SARS-CoV-2 in vitro. Soluble recombinant human ACE2 protein could actually be beneficial as a novel biological therapeutic to combat or limit infection progression caused by coronaviruses that utilize ACE2 as a receptor.

Human ACE2 Blocking Antibodies:
Treatment with blocking anti-ACE2 antibodies disrupts the interaction between virus and receptor, neutralizing the spread of SARS-CoV-2.

Spike S (RBD) Protein:
The CoV spike (S) protein plays the most important role in viral attachment, fusion and entry and serves as a target for development of antibodies, entry inhibitors and vaccines. The soluble recombinant RBD (receptor binding domain) of coronavirus (including SARS-CoV-2) Spike proteins exhibit significantly high binding affinity to ACE2 receptor and could block the binding by competing with the virus. Attachment of recombinant SARS-CoV-2 RBD to ACE2-expressing cells could inhibit the infection to host cells.

SARS-CoV-2 Antibodies:
SARS-CoV2 specific antibodies could cross-react with SARS-CoV-2 proteins, mainly the Spike, but also the envelope, membrane and nucleocapsid proteins, and SARS-CoV-2 induced antisera could cross-neutralize SARS-CoV-2, suggesting the potential to develop SARS-CoV-2 proteins-based vaccines for prevention of SARS-CoV-2 and SARS-CoV infections. Spike (RBD) seems to be a strong immunogenic domain of coronaviruses with a large part of the antibody immune response that is directed against this region.

LITERATURE REFERENCES:

  1. Angiotensin‑converting enzyme 2 (ACE2) as a SARS‑CoV‑2 receptor: molecular mechanisms and potential therapeutic target: H. Zhang, et al.; Intensive Care Med. 46, 586 (2020) (Review)
  2. Therapeutic options for the 2019 novel coronavirus (2019-nCoV): G. Li & E. De Clercq; Nat. Rev. Drug Discov. 19, 149 (2020) (Review)
  3. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor: M. Hoffmann, et al.; Cell (Epub ahead of print) (2020)
  4. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2: J.M. Penninger, et al.; Cell (Preprint) (2020)
  5. Soluble angiotensin-converting enzyme 2: a potential approach for coronavirus infection therapy? D. Batlle, et al.; Clin. Sci. 134, 543 (2020)
Biological Therapeutic Strategies against SARS-CoV-2 and COVID-19