Viroporins

The Rotavirus NSP4 Viroporin Domain is a Calcium-conducting Ion Channel

“…Here, very transient and frequent fluctuations (open time <1 ms) to various open states give rise to a particularly “spiky” recording. Although this type of “spiky” ion channel activity is commonly observed among many viroporins 4 , conductance measurements require that the channel remain in the open state for a duration long enough to determine the current plateau with minimal error due to noise. When the opening transitions last for just a few sample points, it is challenging to make a reliable measurement of the open channel current.…”

“…3 , blue box). While other viroporins have been characterized as having both fast current fluctuations (‘spiky’ activity) and well-defined openings, these two kinetic signatures have rarely (if ever) been demonstrated to occur during the same recording 4 . Further, recordings, such as in Fig.…”

“…Over the years, many viroporins have been studied using classical electrophysiological techniques, primarily by reconstituting synthetic peptides or purified recombinant protein of the viroporin into planar lipid bilayers. With few exceptions, viroporins show low selectivity between K + and Na + , but generally show strong selectivity of monovalent cations over divalent cations like calcium (Ca 2+ ) 4 . Thus, while most viroporins are initially targeted to the endoplasmic reticulum (ER), presumably their low permeability for Ca 2+ prevents depletion of ER Ca 2+ stores.…”

Variations in Orf3a protein of SARS-CoV-2 alter its structure and function

“…It contains 29 open reading frames (Orfs) that encode four structural, sixteen non-structural and nine accessory proteins [ 6 ]. Orf3a is the largest accessory protein of 275 amino acids in SARS-CoV-2 [ 7 ] which is involved in critical steps of viral infection cycle and is required for viral replication, and assembly that determines virulence of SARS-CoV-2 [ 8 ]. Structurally, this protein is a multi-pass membrane protein that forms a homotetrameric viroporin with TRAF, ion channel and caveolin binding domain [ 8 ].…”

“…Orf3a is the largest accessory protein of 275 amino acids in SARS-CoV-2 [ 7 ] which is involved in critical steps of viral infection cycle and is required for viral replication, and assembly that determines virulence of SARS-CoV-2 [ 8 ]. Structurally, this protein is a multi-pass membrane protein that forms a homotetrameric viroporin with TRAF, ion channel and caveolin binding domain [ 8 ]. Functionally, Orf3a has been demonstrated to impact host immune system by activating pro-IL-1β gene expression as well as IL-1β secretion that eventually activates NF-kB signalling and NLRP3 inflammasome and contributes to the generation of cytokine storm [ 9 , 10 ].…”