Khosta-2 Virus: As the world continues to battle Covid-19, a new virus similar to the novel coronavirus has emerged. The virus, called Khosta-2, has been detected in Russian horseshoe bats. Khosta-2 is a sarbecovirus, a type of respiratory virus. The majority of animal sarbecoviruses are only distantly related to known human pathogens and do not infect human cells. Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are examples of sarbecoviruses.
SARS-CoV-2 or novel coronavirus is the causative organism of Covid-19. The spread of sarbecoviruses from animals to humans has resulted in outbreaks such as the ongoing Covid-19 pandemic.
SARS-CoVs are strains of coronaviruses that naturally infect humans, bats, and several Asian mammals, and enter the host cell by binding to the ACE2 receptor. The receptor binding domain (RBD) on sarbecoviruses mediates cell invasion by engaging receptor molecules on the host cell. Khosta-2 is capable of using the ACE2 receptor in human cells to facilitate cell entry, a new study has found.
Researchers from Washington State University and Tulane University School of Medicine in the United States analysed two sarbecoviruses found in Russian horseshoe bats. The study describing the findings was published September 22 in the journal PLOS Pathogens.
What Is Khosta-2?
Khosta-2 is a sarbecovirus discovered in Russia, and has been found to interact with ACE2 receptors, the same entry receptor as SARS-CoV-2.
As part of the study, the researchers created viral pseudotypes, which are particles produced through the combination of viruses and foreign viral envelope proteins. The researchers made viral pseudotypes with a recombinant, SARS-CoV-2 spike encoding for the Khosta-2 RBD.
The RBD from Khosta-2 was found to be capable of using the human ACE2 receptor to facilitate cell entry. Also, the viral pseudotypes were resistant to both SARS-CoV-2 monoclonal antibodies (man-made proteins that act like human antibodies in the immune system) and serum from individuals vaccinated for SARS-CoV-2.
The spike protein from Khosta-2 could infect cells similar to human pathogens using the same entry mechanisms as SARS-CoV-2, but has been found to be resistant to neutralisation by serum from individuals who had been vaccinated against SARS-CoV-2.
Where Was Khosta-2 Identified?
Sarbecoviruses can be classified into different classes based on sequence and functional data. Clade 3 sarbecoviruses are found mostly in African and European bats, contain one deletion (a type of mutation that involves the loss of one or more nucleotides from a segment of DNA), and have recently been found to infect using primarily bat ACE2 receptors. SARS-CoVs are clade 1 viruses, which are identified in Asian bats, contain no deletions and bind to the ACE2 receptor in a host cell.
In late 2020, two clade 3 sarbecoviruses were identified in horseshoe bats (Rhinolophus) in Russia. These are Khosta-1 and Khosta-2, the study said.
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Khosta-1 was identified in Rhinolophus ferrumequinum while Khosta-2 was identified in Rhinolophus hipposideros. The Khosta viruses are divergent from the RBD found in SARS-CoV-1 and SARS-CoV-2, similar to other African and European clade 3 viruses. However, both the Khosta viruses have been found to be capable of infecting human cells using the ACE2 receptor.
Khosta-2 Is Resistant To Existing Covid-19 Vaccines
The researchers prepared viral pseudotypes with a recombinant, SARS-CoV-2 spike encoding for the Khosta-2 RBD. The SARS-CoV-2 spike encoding for the Khosta-2 RBD was found to be resistant to the SARS-CoV-2 RBD-specific monoclonal antibody, Bamlanivimab.
The researchers repeated the pseudotype experiment using serum from individuals vaccinated against Covid-19. They observed that the wild-type SARS-CoV-2 spike was easily inhibited by serum from individuals who received both doses of either the Moderna or Pfizer Covid-19 vaccine. However, the SARS-CoV-2 spike encoding for the Khosta-2 RBD was resistant.
Significance Of The Study
The study showed that just replacing the RBD is sufficient to reduce the efficacy of SARS-CoV-2 spike-directed vaccines. This is because the SARS-CoV-2 spike was neutralised by the serum from vaccinated individuals, but the spike encoding for the Khosta-2 RBD was resistant.
The results demonstrate that new recombinant sarbecoviruses may pose a threat to current SARS-CoV-2 vaccines, the authors note in the study. The findings highlight the urgent need to continue the development of new, and broader-protecting sarbecovirus vaccines.
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