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CN-122011122-A - Polypeptide for inhibiting coronavirus replication and air transmission and application thereof

CN122011122ACN 122011122 ACN122011122 ACN 122011122ACN-122011122-A

Abstract

The invention provides polypeptides that inhibit coronavirus replication and air transmission and uses thereof. Specifically, the invention provides a branched peptide for inhibiting coronavirus replication and air transmission, which comprises a plurality of peptide chain branches taking lysine as a connecting core and being coupled with the connecting core through an amide bond, wherein the sequence of the peptide chain branches is selected from the group consisting of SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 4 or a combination thereof, and the number of the peptide chain branches is equal to or more than 2. The molecular peptide (especially the tetra-branched peptide) can inhibit the replication of coronaviruses and can effectively block the interpersonal transmission of the highly transmissible coronaviruses.

Inventors

  • ZHAO CHANJUN

Assignees

  • 复旦大学

Dates

Publication Date
20260512
Application Date
20260206

Claims (10)

  1. 1. A branched peptide that inhibits coronavirus replication and air transmission, wherein the branched peptide comprises a plurality of peptide chain branches having lysine as a connecting core and coupled to the connecting core via an amide bond, wherein the sequence of the peptide chain branches is selected from the group consisting of SEQ ID No.1, SEQ ID No. 2, SEQ ID No. 4, or a combination thereof; And the number of the peptide chain branches is not less than 2, preferably 2 to 10, more preferably 4 to 8.
  2. 2. The branched peptide of claim 1, wherein the coronavirus is SARS-CoV-2, and wherein the SARS-CoV-2 is a highly transmissible variant selected from the group consisting of B.1.1.63, delta (B.1.617.2), BA.2 and BA.5.
  3. 3. The branched peptide of claim 1, wherein when the sequence of each peptide chain branch is SEQ ID NO:1 and the number of peptide chain branches is 4, the branched peptide is tetra-branched peptide 4PR26, and the tetra-branched peptide 4PR26 has the structure shown in formula I: (I); When the sequence of each peptide chain branch is SEQ ID NO. 2 and the number of the peptide chain branches is 4, the branched peptide is tetra-branched peptide 4H22, and the structure of the tetra-branched peptide 4H22 is shown as the following formula V: (V); When the sequence of each peptide chain branch is SEQ ID NO. 4 and the number of the peptide chain branches is 8, the branched peptide is octabranched peptide 8P9R, and the structure of the octabranched peptide 8P9R is shown in the following formula II: (II)。
  4. 4. The branched peptide of claim 1, wherein the sequence of the peptide chain branch further comprises the sequence set forth in SEQ ID No. 3.
  5. 5. A pharmaceutical composition comprising the branched peptide of claim 1 and a pharmaceutically acceptable carrier.
  6. 6. Use of a branched peptide according to claim 1 or a pharmaceutical composition according to claim 5 in the manufacture of a medicament for inhibiting coronavirus airborne.
  7. 7. The use according to claim 6, wherein the medicament is selected from the group consisting of: (1) For inhibiting coronavirus replication and air transmission; (2) For reducing the risk of an individual infected with coronavirus transmitting the virus to a susceptible individual by the air route; (3) Is used for preventing infection of susceptible individuals by coronavirus through air route.
  8. 8. A kit is characterized in that, the kit comprises: (a) An effective amount of a branched peptide as claimed in claim 1 or a pharmaceutical composition as claimed in claim 5, and (B) Instructions for use of the branched peptide or the pharmaceutical composition for inhibiting air transmission of coronavirus.
  9. 9. A method of screening candidate branched peptides for inhibition of coronavirus airborne function, said method comprising the steps of: (s 1) in a test group, treating coronavirus and infected cells in the presence of a test branched peptide, and determining data of said test group selected from the group consisting of: (a) Number of coronavirus attached to cell A1, and/or (B) Release amount B1 of coronavirus from infected cells; And in a control group, treating coronavirus and infected cells under otherwise identical conditions and in the absence of test branched peptide, and determining data of the control group selected from the group consisting of: (c) Number of attachment A0 of coronavirus to cell attachment, and/or (D) Release amount B0 of coronavirus from infected cells, and (S 2) comparing the number of attachments and/or the number of releases in the test group and the control group, Wherein, if the number of attachment A1 of the test group is significantly higher than the number of attachment A0 of the control group, and/or the number of release B1 of the test group is significantly higher than the number of release B0 of the control group, the above test branched peptide is suggested to be a candidate branched peptide for inhibiting the air-borne function of coronavirus.
  10. 10. A cell surface cross-linking agent comprising the branched peptide of claim 1 for cross-linking a coronavirus particle to the surface of a cell expressing a glycosaminoglycan.

Description

Polypeptide for inhibiting coronavirus replication and air transmission and application thereof Technical Field The invention relates to the field of biological medicine, in particular to a polypeptide for inhibiting coronavirus replication and air transmission and application thereof. Background With the enhancement of viral transmission and the massive increase of infection cases, repeated infections with the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) frequently occur, thereby exacerbating the risk of death and hospitalization. And as SARS-CoV-2 spreads and evolves in the population, the number of basic regenerations (R0) of delta and HMG variants increases several times. The enhancement of the transmission force brings challenges to epidemic prevention and control measures. For influenza, studies have shown that Baxlovir can reduce influenza spread. Then for SARS-CoV-2, there is no similar drug at present. The difficulty in preventing SARS-CoV-2 air transmission is that there are many factors affecting the transmission of coronavirus respiratory viruses, including the replication ability of the virus in the respiratory tract, the viruses carried by asymptomatic and symptomatic infected persons, the individual vaccination conditions, etc. can all affect the transmission of the virus. During viral outbreaks, the spreading capacity of a large number of viruses, the spreading capacity of the SARS-CoV-2 variant, continues to increase, with an increasing number of basic infections (R0) from the original strain to the delta, HMW variant. It is currently known that human angiotensin converting enzyme 2 (ACE 2), the attachment factor heparan sulfate (glycosaminoglycan family member) and other co-receptors play an important role in viral replication and transmission, but these known factors are not yet sufficient to explain why the R0 of the SARS-CoV-2 variant will be higher than the original strain (strain preceding the alpha variant) and SARS-CoV-1. Thus, there is a strong need in the art to develop an antiviral drug that can inhibit the replication of highly transmissible SARS-CoV-2 and block viral air transmission to reduce the risk of transmitted and repeated infections. Disclosure of Invention The invention aims to provide an antiviral drug capable of inhibiting the replication of highly transmissible SARS-CoV-2 and blocking the air transmission of viruses, so as to reduce the damage caused by transmitted infection and repeated infection. In a first aspect of the present invention, there is provided a branched peptide for inhibiting replication and air transmission of coronavirus, said branched peptide comprising a plurality of peptide chain branches having lysine as a connecting core and coupled to said connecting core via an amide bond, wherein the sequence of said peptide chain branches is selected from the group consisting of SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:4, or a combination thereof; And the number of the peptide chain branches is not less than 2, preferably 2 to 10, more preferably 4 to 8. In another preferred embodiment, the sequence of each of said peptide chain branches is independently selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2 or SEQ ID NO: 4. In another preferred embodiment, the coronavirus is SARS-CoV-2. In another preferred embodiment, the SARS-CoV-2 is a highly transmissible variant selected from the group consisting of B.1.1.63, delta (B.1.617.2), BA.2 or BA.5. In another preferred example, when the sequence of each peptide chain branch is SEQ ID NO: 1, the number of peptide chain branches is 4, the branched peptide is the tetra-branched peptide 4PR26. In another preferred embodiment, the structure of the tetra-branched peptide 4PR26 is shown in formula I below: (I)。 In another preferred example, when the sequence of each peptide chain branch is SEQ ID NO: 2, the number of peptide chain branches is 4, the branched peptide is a tetra-branched peptide 4H22. In another preferred embodiment, the tetra-branched peptide 4H22 has the structure of formula V: (V)。 in another preferred example, when the sequence of each peptide chain branch is SEQ ID NO:4, the number of peptide chain branches is 8, the branched peptide is octabranched peptide 8P9R. In another preferred embodiment, the octabranch peptide 8P9R has the structure shown in formula II: (II)。 in another preferred embodiment, the branched peptide further comprises a branched peptide having the sequence shown in SEQ ID NO. 3. In another preferred embodiment, the branched peptide has an inhibition or blocking rate of the coronavirus release of not less than 30%, preferably 50% to 100%, more preferably 75% to 100%. In another preferred embodiment, the branched peptide concentration is 25 μg/mL and the inhibition rate of SARS-CoV-2 virus release is not less than 30%. In a second aspect of the invention there is provided a pharmaceutical composition comprising a branched peptide according to the first aspect o