Today, the research team led by Lisa F P ng of a * star published important research results in the top medical journal The Lancet. < p > < p > they found that in the early stage of the new coronavirus epidemic, there was a new coronavirus variant which lost 382 nucleotides and could not be transcribed by ORF8. Compared with the wild type, this mutant type of new coronavirus had no reduction in replication capacity, but its toxicity was significantly reduced. The systemic release of proinflammatory cytokines in infected patients was less, and the symptoms were lighter. It is understood that the new coronavirus of this mutant type disappeared in March this year.
means that novel coronavirus pneumonia may be a potent target for treating new crown pneumonia. Blocking the protein encoding by ORF8 can reduce the harm of the new crown virus to human body, ORF8. Since the outbreak of the new coronavirus at the end of last year, scientists all over the world have been trying to map the genetic diversity of the new coronavirus and monitor the variation trend of the new coronavirus, especially to identify the mutation with selective advantage. < / P > < p > not long ago, we reported that the number of new coronavirus strains carrying d614g mutation has soared all over the world (especially in Europe and the United States) since its emergence in February this year, and has now replaced the original strain in 2019 as the mainstream virus strain. It has been confirmed that d614g mutation can improve the infection ability of new coronavirus, but the toxicity of mutant virus does not seem to change. < / P > < p > in the process of monitoring the mutation dynamics of the new coronavirus, scientists from Singapore found that a new coronavirus variant with a deletion of 382 nucleotides (Δ 382) appeared in Singapore from January to February this year. The deletion starts at orf7b and ends at the transcriptional regulatory sequence of ORF8. As a result of deletion, the transcription of ORF8 is directly blocked, which means that ORF8 cannot encode protein, but this mutation does not reduce the replication ability of new coronavirus. Although the new coronavirus carrying the Δ 382 mutation was successfully transmitted in the early stage of the outbreak, it was never found again in March this year. Up to now, the function of ORF8 protein is still unclear. However, researchers from the Singapore Institute of science and technology are still interested in this missing variant, because recent preliminary studies have shown that ORF8 protein can mediate immune escape by down regulating the expression of MHC-I molecules; and some researchers have found that ORF8 protein interacts with 47 proteins in human body. Although the mutation of < / P > < p > Δ 382 does not affect the replication of NCV, there is no relevant study on its effect on the clinical results of infected patients and the immune response in vivo.
novel coronavirus pneumonia was recruited by researchers from Singapore Science and Technology Research Bureau. Among them, 131 new crown pneumonia infections were recruited. 92 of them were infected with wild type new crown virus, 29 infected with 382 variant, 10 infected with 382 variant and wild type new crown virus. In general, the gender and complications of the three different infection types were similar. Compared with patients infected with wild-type NCV, the patients infected with △ 382 variant were younger, with lower median body temperature and less systemic inflammation. < p > < p > although the chest X-ray results showed that the incidence of pneumonia in the three groups was similar, but the patients infected with △ 382 variant did not need oxygen treatment, while 3 people in the mixed infection group needed oxygen treatment, accounting for 30%, and 26 people in the wild type infection group, accounting for 28%. After adjusting for age and comorbidities, the above differences still existed (or = 0.07). < p > < p > of the 131 patients mentioned above, 97 patients had retained blood samples, 64 were infected with wild-type virus, 25 were infected with △ 382 variant, and 8 were co infected.
novel coronavirus pneumonia was detected on the eighth day after the onset of symptoms. Compared with those infected with the wild type of new crown virus, the higher concentrations of IFN- gamma were detected in the blood samples of patients with variant 382 new variant of the crown virus, and the lower concentrations of chemokine IP-10 (CXCL10), MCP-1 (CCL2) and MIP-1 beta (CC), which were closely related to severe crown pneumonia. L4) and anti-inflammatory protein IL-1ra. Compared with wild-type NCV infection without pneumonia, T cell activation related cytokines (IFN – γ, TNF – α, IL-2 and IL-5) were up-regulated in patients infected with △ 382 variant and without pneumonia, while growth factors (HGF, LIF and VEGF-A) associated with lung injury were lower. However, previous studies have found that T cell response in patients infected with wild-type new coronavirus is seriously impaired . Generally speaking, patients infected with the △ 382 variant have better clinical outcomes, which should be related to the stronger immune response of the human body to the △ 382 variant. Novel coronavirus pneumonia is a new potential therapeutic strategy for new crown pneumonia. It is worth further exploring that
can combine with recent studies to find that ORF8 protein can down regulate the expression of MHC-I . We can basically confirm that ORF8 protein plays an important role in immune escape of new coronavirus. Therefore, inhibiting the function of ORF8 protein is a potential new strategy for treating coronavirus pneumonia.
, of course novel coronavirus pneumonia is not only helpful to drug research and development, but also helpful to vaccine research and development. The development of vaccine targeting ORF8 protein may limit the development of new crown virus from the very beginning and prevent patients from progressing to severe new crown pneumonia. Finally, to deal with the ever-changing new coronavirus, the constant strategy of human beings should be social isolation, recognition of virus, research and development of drugs and vaccines. The new coronavirus will show its flaws sooner or later.