55 results about "3c protease" patented technology

This application is directed generally to foot-and-mouth disease virus (FMDV) 3C proteases that have been modified by mutating a polynucleotide sequence coding for the FMDV 3C protease. The modified FMDV proteases exhibit proteolytic activity on FMDV P1 precursor protein and exhibit a reduction in one or more toxic or inhibitory properties associated with an unmodified FMDV 3C protease on a host cell used to recombinantly produce it. Vectors carrying polynucleotides encoding modified FMDV 3C protease sequences can induce production of FMDV virus-like particles in a host cell when expressed in the host cell. The modified FMDV 3C proteases can generally be used to produce immunogenic FMDV preparations capable of inducing an immune response against FMDV.

A structure general formula of a caprolactam aldehyde enterovirus 71 (EV 71) 3C protease inhibitor is as shown in chemical combination A, all variables in the structure are defined in an instruction book, and the compound effectively restrains or blocks the copy of the enterovirus 71. The invention relates to a compound with the structure as shown in formula (A), various types of optical isomers of the compound with the structure as shown in formula (A), drug active metabolites, officinal salt, solvate and discovery and application when the compound with the structure as shown in formula (A), the various kinds of optical isomers of the compound with the structure as shown in formula (A), the drug active metabolites and the officinal salt are used for preparing antiviral drugs for curing hand-foot-mouth virus infection diseases. The invention further relates to an intermediate and a synthetic method of preparing the compound with the structure as shown in formula (A).

Novel 1,2,4-thiadiazole compounds are provided, which are effective as inhibitors of cysteine activity-dependent enzymes and in particular of cysteine proteases. The compounds are useful in treating acne by inhibition of transglutaminase, common cold by inhibition of human rhinovirus 3C protease and inflammatory joint disease by inhibition of cathepsins. The compounds of the present invention are 3,5-disubstituted 1,2,4-thiadazole of the general formula (I):where Z is a nitrogen containing group with recognition sequence for the enzyme and Y is a substituent that tunes the reactivity of the inhibitor towards the thiol group of the cysteine activity-dependent enzyme. The Y group may also serve in recognition.

The invention discloses a structure and application of an Enterovirus 71 (EV71) 3C protease and belongs to the field of RNA virus protein. The invention also discloses an application of the 3C protease and a substrate binding groove thereof in drug design. The protein provided by the invention has a special substrate binding groove and new EV71 virus 3C protease drugs are designed according to the spatial structure of the substrate binding groove, thus the inhibitors aiming at the EV71 virus 3C protease, which are more specific and have better effect, can be obtained, potential drug candidates can be provided for the clinical treatment of hand, foot and mouth disease and the EV71 virus 3C protease has very high application value.

The invention discloses a 4-iminooxazolidine-2-ketone enterovirus 71(EV71) 3C protease inhibitor of which the structural general formula is shown as a compound (M), each variable in the structure is defined as the specification, and the compounds are used for effectively inhibiting or stopping the replication of enterovirus 71. The invention relates to discovery and application of a compound with a structure shown as the formula (M) as well as various optical isomers of the compound, a pharmaceutically active metabolite, a medicinal salt, a solvate and a prodrug of the compound in preparation of antiviral drugs for treating hand-foot-mouth virus infection diseases and also relates to an intermediate for preparing the compound with the structure shown as the formula (M) and a synthesis method.

The invention discloses an application of asymmetric aryl disulfide compounds serving as virus 3C protease inhibitors in preparation of antiviral drugs. The structural formula of the compounds is shown in the formula I or the formula II, wherein in the formula I, R1 represents mono-substituted groups or poly-substituted groups on a benzene ring and is independently selected from -NO2, C1-C3 alkyl, C1-C3 alkoxy, R'OCO- and a condensed ring constructed through direct condensation with the benzene ring, R' represents C1-C3 alkyl, R2 represents H or acyl with the number of carbon atoms being 1-3, and R3 represents H or C1-C3 alkyl; in the formula II, X represents NH or S, R4 represents mono-substituted groups or poly-substituted groups on the benzene ring, R1 is independently selected from -NO2, C1-C3 alkyl and halogen, R5 represents H or R''OCO-, R'' represents C1-C3 alkyl, R6 represents H or R''' CONH-, and R''' represents C1-C3 alkyl. The asymmetric aryl disulfide compounds can have an inhibition effect on CVB3 viruses on the cell level by inhibiting the activity of CVB3 3C and has good antiviral drug application prospect.

The invention discloses a recombinant CL7-CVN protein, and a preparation method and applications thereof. The preparation method includes cloning a coding sequence on an expression vector to obtain arecombinant expression vector; and converting the recombinant expression vector into host cells to perform expression and purification so as to obtain the recombinant CL7-CVN protein. Through a synthesized CVN gene and gene assembly method, the fusion expression vector can be built, and the highly soluble expression of the vector in escherichia coli can be realized; and according to the heat resistance of the recombinant CL7-CVN protein and through heat treatment and 3C protease digestion, the recombinant CL7-CVN protein and CVN protein can be rapidly obtained through one-step affinity chromatography, and purity can reach 99%. The provided preparation method can make the recombinant protein expression significantly enhanced, make activity more stable and make a purification method simpler;and both the prepared recombinant CL7-CVN protein and CVN protein have antiviral activity.

The invention discloses a foot-and-mouth disease virus (FMDV) 2C3ABC recombinant protein as well as a preparation method and application thereof, and belongs to the field of pharmaceutical biotechnology. According to the invention, the mutation of the following sites is performed on the basis of an original FMDV 3C protease gene: Cys142-Ser, Cys163-Gly. FMDV recombinant protein 2C3ABC is expressed as an inclusion body in the bacterial cytoplasm, and is subjected to separation, denaturation, renaturation and multi-step purification, to obtain a complete and enzymolysis-free FMDV nonstructural protein mu2C3ABC, wherein the protein has solubility and complete antigenicity, and has a molecular weight of 72 kDa. The protein, as a diagnostic antigen, is prepared into chromatographic strips, has sensitivities of 98.4% and 100% respectively in the detection of FMDV experimentally infected pigs and naturally infection-free pigs, and has specificities of 100% and 98% respectively in the detection of naturally infection-free pigs and vaccine-immunized pigs. Compared with commercial kits Ceditest and UBI, the FMDV 2C3ABC recombinant protein has a high degree of consistency, can be used to distinguish infected animals and immunized animals, wherein K = 0.823 (p is smaller than 0.05).

Compounds of formula (I), wherein the variables of the formula are as defined in the present disclosure, advantageously inhibit or block the biological activity of picornavirus 3C protease. These compounds, and pharmaceutical compositions containing these compounds, are useful for treating patients or hosts infected with one or more picornaviruses, such as RVP. Intermediates and synthetic methods for preparing such compounds are also described.

The invention relates to a recombinant DNA vector for efficiently preparing foot and mouth disease virus-like particles, the foot and mouth disease virus-like particles prepared by utilizing a recombinant expression plasmid vector containing the recombinant DNA vector to transfect a host cell, application thereof and a vaccine. Aiming at the problems of toxicity of 3C protease to the host cell andimpact of 3C protease on yield of foot and mouth disease VLPs, a 3CshRNA segment having disturbing effect on gene expression of 3C protease is designed, so that expression of 3C protease in the process of preparing the foot and mouth disease VLPs is reduced obviously; three sites are mutagenized on the basis of original foot and mouth disease virus 3C protease gene, so that action effect of 3C protease is regulated specifically. Through modifying the 3C protease gene, the toxicity of 3C protease to the host cell is lowered, and effective cutting performance of 3C protease to foot and mouth disease virus P1 precursor protein is improved, so that synthesis yield of the foot and mouth disease VLPs is increased greatly, and a foundation is laid for large-scale production and use of foot and mouth disease VLP vaccines.

Compounds of the formula: 1 where the formula variables are as defined in the disclosure, advantageously inhibit or block the biological activity of the picornaviral 3C protease. These compounds, as well as pharmaceutical compositions containing these compounds, are useful for treating patients or hosts infected with one or more picornaviruses, such as RVP. Intermediates and synthetic methods for preparing such compounds are also described.