1. Anti-infection
  2. CHIKV
  3. CHVB-066

CHVB-066 is an alphavirus non-structural protein nsP1 inhibitor that exhibits varying degrees of inhibitory activity against nsP1 of CHIKV and VEEV. CHVB-066 inhibits MTase and GTase activities and disrupts the capping process of viral RNA, including inhibiting CHIKV replication, reducing progeny viruses, and preventing cytopathic effects. It shows varying degrees of inhibitory activity against nsP1 of CHIKV and VEEV but lacks anti-SFV replication activity, displays cross-resistance with MADTP series compounds, and requires nsP2/nsP3 mutations to develop complete drug resistance. This inhibitor with varying inhibitory activity against nsP1 of CHIKV and VEEV can be widely applied to relevant studies on chikungunya virus infection and chikungunya fever.

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CHVB-066

CHVB-066 Chemical Structure

CAS No. : 1309199-94-7

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Description

CHVB-066 is an alphavirus non-structural protein nsP1 inhibitor that exhibits varying degrees of inhibitory activity against nsP1 of CHIKV and VEEV. CHVB-066 inhibits MTase and GTase activities and disrupts the capping process of viral RNA, including inhibiting CHIKV replication, reducing progeny viruses, and preventing cytopathic effects. It shows varying degrees of inhibitory activity against nsP1 of CHIKV and VEEV but lacks anti-SFV replication activity, displays cross-resistance with MADTP series compounds, and requires nsP2/nsP3 mutations to develop complete drug resistance. This inhibitor with varying inhibitory activity against nsP1 of CHIKV and VEEV can be widely applied to relevant studies on chikungunya virus infection and chikungunya fever[1][2][3][4].

In Vitro

CHVB-066 (Serial dilutions; 96 h) potently inhibits CHIKV replication in Vero E6 cells with an EC50 of 0.6 μM and has a CC50 of 25 μM, with no activity against SFV[1].
CHVB-066 (0.5-32 μM; 30 min) dose-dependently inhibits the combined methyltransferase and guanylyltransferase enzymatic activity of purified wild-type CHIKV nsP1 at concentrations ranging from 0.5 to 32 μM[1].
CHVB-066 (0.16-5.00 μM; 48 h) induces a dose-dependent reduction in CHIKV 899 viral RNA and infectious progeny production in Vero cells, with a significant >4-log10 reduction at 5.00 μM after 48 h[2].
CHVB-066 (0-12.5 μM; 4 days) inhibits wild-type rCHIKV LS3 replication in Vero E6 cells with an EC50 of 0.65 μM; resistance requires the combined nsP1S454G and nsP1W456R mutations, with maximum resistance (18.5-fold) achieved when combined with nsP2M703T and nsP3L494P mutations[2].
CHVB-066 (0.5-1000 μM) potently inhibits the guanylyltransferase activity of purified VEEV nsP1 with an IC50 of <0.5 μM[2].
CHVB-066 (0.001-100 μM) inhibits the methyltransferase activity of purified VEEV nsP1 with an IC50 of 1.9 μM[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Cytotoxicity Assay[1]

Cell Line: Vero E6 cells
Concentration: Serial dilutions
Incubation Time: 96 h
Result: Inhibited CHIKV-induced CPE with a 50% effective concentration (EC50) of 0.6 μM.
Exhibited a 50% cytotoxic concentration (CC50) of 25 μM.
Showed no antiviral activity against Semliki Forest virus (SFV).\nRendered CHIKV nsP1-P34S and CHIKV nsP1-S454G+W456R mutants completely resistant, with an EC50 of >12.5 μM and a fold resistance of 20.8 compared to wild-type CHIKV.
Maintained activity against CHIKV nsP1-G230R+K299E mutant, with an EC50 of 0.3 μM and a fold resistance <1.

Real Time qPCR[2]

Cell Line: Vero cells
Concentration: 0.16-5.00 μM
Incubation Time: 48 h
Result: Caused a marked dose-dependent reduction in CHIKV 899 viral genome copies and infectious virus progeny.
Induced a significant >4-log10 reduction in both viral RNA and infectious virus yield at 5.00 μM compared to untreated controls.
Molecular Weight

339.43

Formula

C19H25N5O

CAS No.
SMILES

O=C(N1CCN(CC1)C2=NC(NCC)=NC(C)=C2)C3=CC=C(C)C=C3

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    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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CHVB-066
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HY-184264
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