SARS-CoV-2: Recent Variants and Clinical Efficacy of Antibody-Based Therapy

Abstract

Multiple variants of SARS-CoV-2 have emerged and are now prevalent at the global level. Currently designated variants of concern (VOCs) are B.1.1.7, B1.351, P.1, B.1.617.2 variants and B.1.1.529. Possible options for VOC are urgently required as they carry mutations in the virus spike protein that allow them to spread more easily and cause more serious illness. The primary targets for most therapeutic methods against SARS-CoV-2 are the S (Spike) protein and RBD (Receptor-Binding Domain), which alter the binding to ACE2 (Angiotensin-Converting Enzyme 2). The most popular of these strategies involves the use of drug development targeting the RBD and the NTD (N-terminal domain) of the spike protein and multiple epitopes of the S protein. Various types of mutations have been observed in the RBDs of B.1.1.7, B1.351, P. and B.1.620. The incidence of RBD mutations increases the binding affinity to the ACE2 receptor. The high binding affinity of RBD and ACE2 has provided a structural basis for future evaluation of antibodies and drug development. Here we discuss the variants of SARS-CoV-2 and recent updates on the clinical evaluation of antibody-based treatment options. Presently, most of the antibody-based treatments have been effective in patients with SARS-CoV-2. However, there are still significant challenges in verifying independence, and the need for further clinical evaluation.

Potent human broadly SARS-CoV-2–neutralizing IgA and IgG antibodies effective against Omicron BA.1 and BA.2

“…Adjunct to its neutralizing activity, the strong ADCP potential of Cv2.1169 IgG antibodies could contribute to eliminating cell-free and cell-associated virions and stimulating adaptive immunity via vaccinal effects ( Corti et al, 2021 ). Taking into account the healthcare benefits afforded by antibody therapies to fight COVID-19 ( Corti et al, 2021 ; Singh et al, 2022 ) and considering the excellent antiviral attributes of Cv2.1169 and Cv2.3194, these two antibodies represent promising candidates for prophylactic and/or therapeutic strategies against COVID-19. Long-acting versions of these broadly SARS-CoV-2–neutralizing antibodies with extended half-life could be used to provide protective immunity in immunocompromised populations ( Gentile and Schiano Moriello, 2022 ).…”

A Novel Human Neutralizing mAb Recognizes Delta, Gamma and Omicron Variants of SARS-CoV-2 and Can Be Used in Combination with Sotrovimab

“…The novel SARS-CoV-2 virus is spreading at an extremely fast pace worldwide, leading to the rapid generation of new variants, which show resistance to the available mAb-based therapies [ 1 , 2 , 8 ]. In particular, the efficacy of mAbs targeting the RBM domain of the Spike protein, approved for the treatment of COVID-19 [ 18 ], has been found decreased (with the exception of Sotrovimab) especially in the case of the Omicron variant [ 19 , 20 , 21 ].…”

“…On January 2020, a novel pneumonia virus, expanding abruptly worldwide, was identified and named 2019 novel coronavirus (2019-nCoV) [ 1 , 2 ] or SARS-CoV-2. The latter is a highly transmissible virus, which mainly affects the respiratory system, by infecting the cells through the Angiotensin Converting Enzyme-2 (ACE-2) in human hosts, which binds to the Spike-Receptor Binding Domain (RBD) protein of the coronavirus.…”

Potent Human Broadly SARS-CoV-2 Neutralizing IgA and IgG Antibodies Effective Against Omicron BA.1 and BA.2

“…Adjunct to its neutralizing activity, the strong ADCP potential of Cv2.1169 IgG antibodies could contribute to eliminating cell-free and cell-associated virions and stimulating adaptive immunity via vaccinal effects (Corti et al, 2021). Taking into account healthcare benefits afforded by antibody therapies to fight COVID-19 (Corti et al, 2021; Singh et al, 2022), and considering the excellent antiviral attributes of Cv2.1169 and Cv2.3194, these two antibodies represent promising candidates for prophylactic and/or therapeutic strategies against COVID-19. Long-acting versions of these broadly SARS-CoV-2 neutralizing antibodies with extended half-life could be used to provide protective immunity in immunocompromised populations (Gentile and Schiano Moriello, 2022).…”