Vikash Kumar

Cryptochromes are blue light receptors that mediate circadian rhythm and magnetic sensing in various organisms. A typical cryptochrome consists of a conserved photolyase homology region domain and a varying carboxyl-terminal extension across species. The structure of the flexible carboxyl-terminal extension and how carboxyl-terminal extension parti...

The δ-opioid receptor (DOR) is a critical pharmaceutical target for pain management. Although the high-resolution crystal structures of the DOR with both agonist and antagonist have recently been solved, the activation mechanism remains to be elusive. In this study, a DOR agonist ADL5859 was docked to the inactive DOR and multiple microsecond molec...

Flexible regions in biomolecular complexes, although crucial to understanding structure–function relationships, are often unclear in high-resolution crystal structures. In this study, we showed that single-molecule techniques, in combination with computational modeling, can characterize dynamic conformations not resolved by high-resolution structur...

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causing agent of the COVID-19 pandemic. Angiotensin-converting enzyme 2 (ACE2) has been identified as the host cell receptor that binds to the receptor-binding domain (RBD) of the SARS-COV-2 spike protein and mediates cell entry. Because the ACE2 proteins are widely available i...

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused worldwide pandemic and is responsible for millions of worldwide deaths due to -a respiratory disease known as COVID-19. In the search for a cure of COVID-19, drug repurposing is a fast and cost-effective approach to identify anti-COVID-19 drugs from existing drugs. The receptor...

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causing agent of the COVID-19 pandemic, has spread globally. Angiotensin-converting enzyme 2 (ACE2) has been identified as the host cell receptor that binds to receptor-binding domain (RBD) of the SARS-COV-2 spike protein and mediates cell entry. Because the ACE2 proteins are wid...

G-protein-coupled receptors (GPCRs) transmit signals into the cell in response to ligand binding at its extracellular domain, which is characterized by coupling of agonist induced receptor conformational change to guanine nucleotide (GDP) exchange with GTP on a heterotrimeric (αβγ) guanine nucleotide-binding protein (G-protein), leading to the acti...

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19, is spreading globally and has infected more than 3 million people. It has been discovered that SARS-CoV-2 initiates the entry into cells by binding to human angiotensin-converting enzyme 2 (hACE2) through the receptor binding domain (RBD) of its s...

The ovarian tumor domain (OTU) deubiquitinylating cysteine proteases OTU ubiquitin aldehyde binding 1 (OTUB1) and OTUB2 are representative members of the OTU subfamily of deubiquitinylases. Deubiquitinylation critically regulates a multitude of important cellular processes, such as apoptosis, cell signaling, and growth. Moreover, elevated OTUB expr...

Over the last few decades, anticancer peptides (ACPs) have turned into potential warheads against cancer. Apart from small molecules and monoclonal antibodies, ACPs have been proven to be effective against cancer cells. ACPs are small cationic peptides that selectively bind to the negatively charged cancer cell membrane and kill them by various mec...

Development of a suitable vaccine against visceral leishmaniasis (VL), a fatal parasitic disease, is considered to be vital for maintaining the success of kala-azar control programs. The fact that Leishmania-infected individuals generate life-long immunity offers a viable proposition in this direction. Our prior studies demonstrated that T-helper1...

Deubiquitinylases (DUBs) are highly specialized enzymes which are responsible for removal of covalently attached ubiquitin(s) from the targeted proteins. DUBs play an important role in maintaining the protein homeodynamics. Recently, DUBs have emerged as novel therapeutic targets in cancer, inflammation, diabetes, and neurodegeneration. Among the d...

Phosphoinositide-3-kinases (PI3Ks) are members of a large family of serine threonine kinases, which participate in important cellular events like cell survival, growth and proliferation. Among three classes, Class II PI3Ks have not been thoroughly investigated for their role in PI3K mediated signaling. In Class II PI3Ks, particularly PI3KC2α and PI...

In this study, a series of coumarin-indole hybrids have been synthesized and evaluated for their lipid lowering activity. Preliminary biological screening of the synthesized compounds was undertaken in an in vitro model of the HMG-CoA reductase enzyme, and the activity was confirmed in Triton WR-1339 induced hyperlipidemic rats. Among the hybrids,...

The synergistic combination of two catalysts is an emerging strategy towards the formation of unprecedented complex molecules, and herein bovine serum albumin (BSA) and the neutral ionic liquid 1-butyl-3-methylimidazolium bromide ([bmim]Br) are used together for the first time towards multiple C−C and C−S bond-formation reactions in one pot under m...

RNA Polymerase II (RNAPII) uniquely possesses an extended carboxy terminal domain (CTD) on its largest subunit, Rpb1, comprising a repetitive Tyr1Ser2Pro3Thr4 Ser5Pro6Ser7 motif with potential phosphorylation sites. The phosphorylation of the CTD serves as a signal for the binding of various transcription regulators for mRNA biogenesis including th...

Correct termination of protein synthesis would be a critical step in translation of organellar ORFs of the apicoplast and mitochondrion of the malaria parasite. We identify release factors (RFs) responsible for recognition of the UAA and UGA stop- codons of apicoplast ORFs and the sole UAA stop-codon that terminates translation from the three mitoc...

Coinfections are common in natural populations and the outcome of their interactions depends on the immune responses of the host elicited by the parasites. Earlier we showed that immunization with BmAFII (Sephadex G-200 eluted) fraction of human lymphatic filaria Brugia malayi inhibited progression of Leishmania donovani infection in golden hamster...

Aberrant epigenetic control is a common phenomenon in tumour progression. The epigenetic modifications such as DNA methylation, histone modification and nucleosome remodelling are involved in the regulation of many biological processes, alteration in which can result into tumourogenesis. Histone acetylation is often associated with gene expression;...

Stereoselectivities of electrophilic additions of molecular iodine to enantiomerically pure highly functionalized allylic alcohols with internal nucleophiles have been investigated. The intramolecular nucleophilic attack to I2-∏ complex by oxygen nucleophile to obtain tri- and tetrasubstituted THFs are highly regio-, stereoselective and substrate c...

We have synthesized new fluconazole analogues containing two different 1,2,3-triazole units in the side chain. Synthesis of new amide analogues by using a variety of acids is also described. All the compounds showed very good antifungal activity. Hemolysis study of the most active compounds 6e and 13j showed that both compounds did not cause any he...

Isocitrate lyase (ICL), is a key enzyme of the glyoxylate shunt crucial for the survival of Mycobacterium tuberculosis (Mtb) in macrophages during persistent infection. MtbICL catalyses the first step of this carbon anaplerosis cycle and is considered as a potential anti-tubercular drug target. The MtbICL is a tetramer with 222 symmetry, and each s...

Kinases are one of the major players in cancer development and progression. Serine threonine kinases such as human checkpoint kinase-1 (Chk1), Mek1 and cyclin-dependent kinases have been identified as promising targets for cancer treatment. Chk1 is an important kinase with vital role in cell cycle arrest and many potent inhibitors targeted to Chk1...

In the search for effective multifunctional agents for the treatment of Alzheimer’s disease (AD), a series of novel hybrids incorporating benzofuran and chalcone fragments were designed and synthesized. These hybrids were screened by using a transgenic Caenorhabditis elegans model that expresses the human β-amyloid (Aβ) peptide. Among the hybrids i...

Visceral leishmaniasis (VL) or kala-azar, a vector-borne protozoan disease, shows endemicity in larger areas of the tropical, subtropical and the Mediterranean countries. WHO report suggested that an annual incidence of VL is nearly 200,000 to 400,000 cases, resulting in 20,000 to 30,000 deaths per year. Treatment with available anti-leishmanial dr...

Aberrant chromosome segregation defects can lead to aneuploidy, a common characteristic of human solid tumors. Aneuploidy is generated due to defects in the mitotic spindle or due to inefficient mitotic checkpoint response. We have isolated a novel mutant allele of wat1, a WD repeat containing protein that exhibits conditional synthetic lethality w...

Thymidylate kinase (TMK) is a potential chemotherapeutic target because it is directly involved in the synthesis of deoxythymidine triphosphate, which is an essential component for DNA synthesis. The gene encoding thymidylate kinase of Brugia malayi was amplified by PCR and expressed in Escherichia coli. The native molecular weight of recombinant B...

Th1 immune responses play an important role in controlling Visceral Leishmaniasis (VL) hence, Leishmania proteins stimulating T-cell responses in host, are thought to be good vaccine targets. Search of such antigens eliciting cellular responses in Peripheral blood mononuclear cells (PBMCs) from cured/exposed/Leishmania patients and hamsters led to...

Azole and carbodithioate hybrids were synthesized as alkyl 1H-azole-1-carbodithioates (7–27) and evaluated for spermicidal/microbicidal activities against human sperm, Trichomonas vaginalis and Candida species. Seventeen compounds (7-14, 16-18 and 20-25) showed spermicidal activity at MEC 1.0% (w/v) and permanently immobilized 100% normal human spe...

Viral diseases have been affecting the human race since ancient times. Currently, a long list of diseases caused by the viruses is available and extensive research in this area has resulted in understanding the finest details of the molecular mechanism of pathogenesis caused by these pathogens. Side by side, efforts have been made towards the searc...

ABSTRACT Licochalcone A (I) isolated from the roots of Chinese licorice, is the most promising antimalarial compound reported so far. In continuation of our drug discovery program, we isolated two similar chalcones, medicagenin (II) and munchiwarin (III), from Crotalaria medicagenia, which exhibited antimalarial activity against Plasmodium falcipar...

Drug resistance to established antifungals such as azole derivatives (fluconazole and ketoconazole) is driving the rise in global mortality due to fungal infection. Identification of new molecular entities structurally unrelated to these may represent a valid strategy to overcome resistance to currently available drugs. In an effort to develop high...

Fluconazole based novel mimics containing 1,2,3-triazole were designed and synthesized as antifungal agents. Their antifungal activities were evaluated in vitro by measuring the minimal inhibitory concentrations (MICs). Compounds 12, 15, and 16 were found to be more potent against Candida fungal pathogens than control drugs fluconazole and amphoter...

Lignin, a major constituent of plant call wall, is a phenolic heteropolymer. It plays a major role in the development of plants and their defense mechanism against pathogens. Therefore Lignin biosynthesis is one of the critical metabolic pathways. In lignin biosynthesis, the Cinnamoyl CoA reductase is a key enzyme which catalyzes the first step in...

Caffeoyl coenzyme A-O-methyltransferases (CCoAOMTs) which are characterized under class I plant OMTs, methylates CoA thioesters, with an in vitro kinetic preference for caffeoyl CoA. CCoAOMTs exhibit association with lignin biosynthesis by showing a prime role in the synthesis of guaiacyl lignin and providing the substrates for synthesis of syringy...