Compositions and methods for treating SARS-CoV-2 infections
The present application relates to methods and compositions and methods for treating viral infections, especially those caused by SARS-CoV-2. In one aspect, a method of treatment comprises administering to a subject in need of such treatment an effective amount of a pharmaceutical composition comprising a multipartite SARS-CoV-2-inhibiting peptide comprising a secretion modulating region (VI-SMR) peptide from HIV-1 Nef in combination with a cell-penetrating peptide (CPP) domain, a Clusterin (Clu)-binding peptide (Clu-BP) domain, a mitochondrial targeting (Mito-T) peptide domain, an anti-fusogenic (AF) peptide domain, a viral attachment inhibitor (VAI) domain or combination thereof, optionally where the SARS-CoV-2-inhibiting peptide is pegylated and/or modified with one or more hydrophobic domains.
1. A multipartite SARS-CoV-2-inhibiting peptide comprising:
an SMR peptide from HIV-1 Nef;
a CPP, Clu-BP, Mito-T-peptide, or combination thereof, and
an AF peptide sequence.
2. The peptide of claim 1 , wherein the SMR peptide comprises the amino acid sequence of VGFPVAAVGFPV (SEQ ID NO: 2), VGFPVAAVGFPVGRKKRRQRRRPPQ (SEQ ID NO: 4) or VGFPVAAVGFPVAAHPLSKHPYWSQPAAHPLSKHPYWSQP (SEQ ID NO: 48).
3. The peptide of claim 1 , wherein the SARS-CoV-2-inhibiting peptide is pegylated, conjugated to a fatty acid, or both.
4. The peptide of claim 1 , wherein the SARS-CoV-2-inhibiting peptide is a dimeric or multimeric peptide.
5. An exosome comprising the SARS-CoV-2-inhibiting peptide of claim 1 .
6. A multipartite SARS-CoV-2-inhibiting peptide comprising:
an SMR peptide from HIV-1 Nef;
a CPP, Clu-BP, Mito-T-peptide, or combination thereof, and
a VAI peptide.
7. The peptide of claim 6 , wherein the SMR peptide comprises the amino acid sequence of VGFPVAAVGFPV (SEQ ID NO: 2), VGFPVAAVGFPVGRKKRRQRRRPPQ (SEQ ID NO: 4) or VGFPVAAVGFPVAAHPLSKHPYWSQPAAHPLSKHPYWSQP (SEQ ID NO: 48).
8. The peptide of claim 6 , wherein the SARS-CoV-2-inhibiting peptide is pegylated, conjugated to a fatty acid, or both.
9. The peptide of claim 6 , wherein the SARS-CoV-2-inhibiting peptide is a dimeric or multimeric peptide.
10. An exosome comprising the SARS-CoV-2-inhibiting peptide of claim 6 .
11. A multipartite SARS-CoV-2-inhibiting peptide comprising:
an SMR peptide from HIV-1 Nef; and
a Mito-T-peptide.
12. The peptide of claim 11 , wherein the SMR peptide comprises the amino acid sequence of VGFPVAAVGFPV (SEQ ID NO: 2), VGFPVAAVGFPVGRKKRRQRRRPPQ (SEQ ID NO: 4) or VGFPVAAVGFPVAAHPLSKHPYWSQPAAHPLSKHPYWSQP (SEQ ID NO: 48).
13. The peptide of claim 11 , wherein the SARS-CoV-2-inhibiting peptide is pegylated, conjugated to a fatty acid, or both.
14. The peptide of claim 11 , wherein the SARS-CoV-2-inhibiting peptide is a dimeric or multimeric peptide.
15. An exosome comprising the SARS-CoV-2-inhibiting peptide of claim 11 .