Although it is necessary to microscope to be able to see them, they are able to combat one of the possible infectious threats budding. These are the molecules developed by researchers from the Higher Scientific Research Council (CSIC) through 3D design computations techniques to combat the next variants of covid. Having been designed using the cellular receptor for the virus -ACE2- as a template, these peptides, called miniACE2they might also be able to neutralize any other new strains of the virus that could arise in the future, especially those with vaccine escape.
The main advantages of this finding, published in the International Journal of Molecular Sciences, are based on the versatility of these peptides to be incorporated into upper respiratory inhalation systems and in chimeric antigen receptors (CAR) that would use the miniACE2 peptide sequence to target the infected cells due to Covid-19. Furthermore, miniACE2 peptides may also have the potential to neutralize new viruses of the Sarbecovirus family or even other coronaviruses that use the same receptor, underlining the potential of miniACE2 peptides as broad-spectrum pan-coronaviral inhibitors.
After the mass vaccination of the world population compared to early variants of SARS-CoV-2there are some possible threats that still remain outstanding. The research, the result of collaboration between scientists from Severo Ochoa Molecular Biology Center (CBM-CSIC-UAM) and the District Institute of Science, Biotechnology and Innovation in Health (Idcbis), in Colombia, allows establishing a early response system since these peptides can be used against new epidemics in the futureand at the same time, constitute a solution for the current cases that vaccines have not covered.
In fact, these types of molecules would help protect patients who have not been able to be vaccinated against covidsuch as immunocompromised people, in addition to constituting a weapon against the emergence of variants of the virus that may escape prior vaccine protection, and even new viruses from the same family for those who vaccines are ineffective.
The synergy between 3D computational design and in vitro techniques. has made it possible to join different parts of the structure of the ACE2 cellular receptor to generate a series of fragments with the capacity to bind to the SARS-CoV-2 spike. Also using computational systems, each of these peptides has been subjected to molecular dynamics simulation against the viral spike, choosing those that showed a more favorable theoretical binding energy. Once selected, these peptides have been synthesized in vitro and have been tested against the viral antigen of new variants in circulation. At least two of the peptides tested showed very promising results, being capable of neutralizing viral infectivity.
Covid adaptation capacity
The concern for rapid evolution of the virus driven by the genetic mutationsviral recombination and selective immune pressure has caused a decrease in the effectiveness of prophylactic measures, like the vaccines and monoclonal antibodiesagainst the new variants of covid. Although cellular memory mediated by T cells confers cross-protection against the new Omicron subvariants, the appearance of mutations associated with L455S and F456L in the current circulating variants BA.2.86, JN.1, KP2, KP3, and LB.1, continues to raise new alarms after exhibiting a “extensive immune evasion and is associated with a potential infection of lung cells.” Thus, although vaccines have reduced the fatality rate of covid to 0.9 percent in October 2024, the continuous evolution of the viruscon emerging variants that exhibit extensive immunological evasion, challenges the effectiveness of current vaccines. Therefore, researchers from both continents emphasize, especially in light of these results, the importance of developing broad-spectrum therapeutic strategies against variants of SARS-CoV-2.
And the fact is that current policies, as highlighted by the scientists participating in this study entitled ‘Design of miniACE2 with enhanced in vitro neutralization activity against SARS-CoV-2’are “effective against a limited number of variants, requiring repeated investment of resources to maintain adequate protection, particularly for at-risk populations such as immunocompromised individuals.”
Furthermore, “the limited applicability of monoclonal antibodies” as emergency tool against virus Due to the high mutation rate, it highlights the need to continue developing and testing biological models for use in emergencies. “As the coronavirus continues to adapt, the possibility of future outbreaks remains“they warn.
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