Compositions and methods for inhibiting viral entry
The invention provides methods, compositions, and kits featuring agents that inhibit viral entry mediated by T-cell Immunoglobulin and Mucin-domain containing proteins (TIM proteins) and other phosphatidylserine receptors.
1. A method for inhibiting viral entry of an enveloped virus to a cell, comprising contacting the cell with an effective amount of an agent that inhibits viral entry via a T-cell Immunoglobulin and Mucin-domain containing protein 1 (TIM-1), TIM3, TIM4 or phosphatidylserine (PS) receptor, wherein the agent consists of an inhibitory nucleic acid molecule or an antibody or fragment thereof, 1,2-diacyl-sn-glycero-3-phospho-L-serine (PS), 1,2-diacyl-sn-glycero-3-phosphoethanolamine (PE) and a liposome consisting of 1, 2-diacyl-sn-glycero-3-phospho-L-serine (PS) and 1,2-diacyl-sn-glycero-3-phosphocholine (PC), wherein the enveloped virus is an alphavirus, flavivirus, filovirus, or arenavirus.
2. The method of claim 1 , wherein the inhibitory nucleic acid molecule is selected from the group consisting of an antisense molecule, an siRNA, and an shRNA.
3. The method of claim 1 , wherein the antibody or fragment thereof that selectively binds to the TIM-1, TIM3 or TIM4.
4. The method of claim 3 , wherein the antibody is a monoclonal or polyclonal antibody.
5. The method of claim 1 , wherein the agent reduces viral entry by at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%.
6. The method of claim 1 , wherein the agent protects the cell from lethality.
7. The method of claim 1 , wherein the virus is selected from the group consisting of Ebola virus (EBOV), Marburg virus (MARY), Amapari virus (AMAV), Tacaribe virus (TCRV), Junin virus (JUNV), Machupo virus (MACV), Chikungunya virus (CHKV), Eastern equine encephalitis virus (EEEV), Dengue virus (DENV), West Nile virus (WNV), Sinbis virus (SINN) or Ross River virus (RRV).