A team of scientists from Germany has determined the effectiveness of current pharmacotherapy in the treatment of more recent variants of severe respiratory coronavirus syndrome 2 (SARS-CoV-2), which including the B.1.1.7 (UK), B.1.351 (South Africa) and B.1.1.248 (Brazil) variations. Their findings indicate that both B.1.351 and B.1.1.248 mutations are capable of overcoming humoral immune responses induced by therapeutic antibodies, vaccines, or SARS-CoV-2 infection. natural. The study is currently available on the bioRxiv* preprint server.
Background
Since its inception in December 2019, the highly contagious and deadly SARS-CoV-2, the causative pathogen of coronavirus disease 2019 (COVID-19), has infected more than 108 million people and more than 2.3 million lives get across the globe. In a global effort to control viral transmission, many studies have been conducted to find effective therapeutic strategies against COVID-19. Currently, several reconstituted antiviral medications and therapeutic antibodies are used to treat COVID-19 emergency patients. As a precautionary measure, some vaccines that may target the viral spike protein have received emergency use approval from concerned authorities.
In the later stages of the pandemic, several new variants of SARS-CoV-2 have emerged, including B.1.1.7 (UK), B.1.351 (South Africa), and B.1.1.248 (Brazil). ). Several mutations found in spike proteins of these variants have been found to significantly increase their susceptibility. In addition, there are preliminary studies that suggest that these changes may be more dynamic and tend to increase the COVID-19-related mortality rate. Because most currently available therapeutic antibodies and vaccines target specifically the SARS-CoV-2 spike protein, there are potential concerns about the efficacy of conventional therapeutic interventions. in preventing the spread and lethality of newly emerged changes.
In the current study, the scientists have evaluated the effectiveness of viral entry inhibitors, monoclonal antibodies, and vaccines in disease prevention with the UK, South Africa, and Brazil variants of SARS-CoV -2.
Study design
The scientists used both human and animal cell lines for behavior in vitro tests. To investigate the efficacy of viral entry inhibitors against the SARS-CoV-2 variants, they used angiotensin-converting enzyme 2 (ACE2) inhibitors, cell protease inhibitors (TMPRSS2), and membrane fusion inhibitors. (EK1 and EK1C4). To determine whether these changes counteract host humoral immune responses, the scientists analyzed the efficacy of anti-SARS-CoV-2 antibodies obtained from three different types of sources: 1) therapeutic monoclonal antibodies (Casirivimab, Imdevimab, and Bamlanivimab); 2) plasma samples collected from patients with severe COVID-19 crisis; and 3) serum samples collected from people who received the BioNTech / Pfizer vaccine (BNT162b2).
Important comments
Although there is evidence showing a greater shift of recently emerged SARS-CoV-2 mutations, the scientists of the current study did not observe significant differences in host cell entry dynamics between its wildtype virus and changes in the UK, South Africa and Brazil. In particular, the spike proteins of wildtype and all test variants of SARS-CoV-2 showed comparable efficacy in entry into host cells.
Interestingly, the entry of both wildtype and mutated species into the host cell was significantly inhibited by soluble ACE2, TMPRSS2 inhibitor, and membrane fusion protectors. Compared with the wildtype virus, the variables showed that they were more prone to ACE2-mediated diffuse inhibition. Similarly, the Brazilian variable showed higher vulnerability to membrane fusion protectors. These observations indicate that viral entry blockers may be used to prevent infections mediated by variable variants of SARS-CoV-2.
Despite showing the dynamics of host cell-virus interactions, significant differences in median neutralization occurred between the wildtype virus and the mutated variables. Among monoclonal antibodies tested, Imdevimab showed comparative efficacy in inhibiting host cell entry with all viral variants. In contrast, both South Africa and Brazil showed partial and total opposition to Casirivimab and Bamlanivimab. However, all antibodies tested showed high potency in inhibiting UK variants.
Neutral antibodies formed in response to SARS-CoV-2 infection are expected to provide protection against relapse. To determine the effectiveness of convalescent plasma treatment against viral changes, plasma samples obtained from COVID-19 patients with wildtype spike protein neutralization efficacy were tested against all viral variants. The findings showed that host cell entry through spike proteins in South African and Brazilian variants was not as effectively inhibited by the majority of plasma samples tested. This shows that people who were previously infected with SARS-CoV-2 viruses are only partially protected against changes in South Africa and Brazil.
In terms of vaccine-mediated protection, the findings showed that the majority of serum samples obtained from people with BNT162b2 vaccine had lower efficacy in inhibiting spike host cell entry compared with the vaccine. those seen for the wildtype SARS-CoV-2 and the RA variant.
Investigate meaning
The study reveals that conventional therapeutic interventions are less effective in preventing changes in South Africa and Brazil of SARS-CoV-2, and therefore, strict implementation of control measures or -medicine to induce the transmission.
* Important message
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical / behavioral practice, or treated as fixed information.