Alexei P. Donchenko

Bio: Alexei P. Donchenko is an academic researcher from USSR Academy of Medical Sciences. The author has contributed to research in topics: RNA & Proteases. The author has an hindex of 9, co-authored 15 publications receiving 2756 citations.

Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes

Abstract: In the course of systematic analysis of protein sequences containing the purine NTP-binding motif, a new superfamily was delineated which included 25 established or putative helicases of Escherichia coli, yeast, insects, mammals, pox- and herpesviruses, a yeast mitochondrial plasmid and three groups of positive strand RNA viruses. These proteins contained 7 distinct highly conserved segments two of which corresponded to the "A" and "B" sites of the NTP-binding motif. Typical of the new superfamily was an abridged consensus for the "A" site, GxGKS/T, instead of the classical G/AxxxxGKS/T. Secondary structure predictions indicated that each of the conserved segments might constitute a separate structural unit centering at a beta-turn. All previously characterized mutations impairing the function of the yeast helicase RAD3 in DNA repair mapped to one of the conserved segments. A degree of similarity was revealed between the consensus pattern of conserved amino acid residues derived for the new superfamily and that of another recently described protein superfamily including a different set of prokaryotic, eukaryotic and viral (putative) helicases.

Coronavirus genome: prediction of putative functional domains in the non-structural polyprotein by comparative amino acid sequence analysis

Abstract: Amino acid sequences of 2 giant non-structural polyproteins (F1 and F2) of infectious bronchitis virus (IBV), a member of Coronaviridae, were compared, by computer-assisted methods, to sequences of a number of other positive strand RNA viral and cellular proteins. By this approach, juxtaposed putative RNA-dependent RNA polymerase, nucleic acid binding ("finger"-like) and RNA helicase domains were identified in F2. Together, these domains might constitute the core of the protein complex involved in the primer-dependent transcription, replication and recombination of coronaviruses. In F1, two cysteine protease-like domains and a growth factor-like one were revealed. One of the putative proteases of IBV is similar to 3C proteases of picornaviruses and related enzymes of como- nepo- and potyviruses. Search of IBV F1 and F2 sequences for sites similar to those cleaved by the latter proteases and intercomparison of the surrounding sequence stretches revealed 13 dipeptides Q/S(G) which are probably cleaved by the coronavirus 3C-like protease. Based on these observations, a partial tentative scheme for the functional organization and expression strategy of the non-structural polyproteins of IBV was proposed. It implies that, despite the general similarity to other positive strand RNA viruses, and particularly to potyviruses, coronaviruses possess a number of unique structural and functional features.

N-terminal domains of putative helicases of flavi- and pestiviruses may be serine proteases

Abstract: Recently we tentatively identified, by sequence comparison, central domains of the NS3 proteins of flaviviruses and the respective portion of the pestivirus polyprotein as RNA helicases (A.E.G. et al., submitted). Alignment of the N-proximal domains of the same proteins revealed conservation of short sequence stretches resembling those around the catalytic Ser, His and Asp residues of chymotrypsin-like proteases. A statistically significant similarity has been detected between the sequences of these domains and those of the C-terminal serine protease domains of alphavirus capsid proteins. It is suggested that flavivirus NS3 and the respective pestivirus protein contain at least two functional domains, the N-proximal protease and the C-proximal helicase one. The protease domain is probably involved in the processing of viral non-structural proteins.

Flaviviridae :T he Viruses and Their Replication

Abstract: FLAVIVIRUSES 1103 Background and Classification 1103 Structure and Physical Properties of the Virion 1104 Binding and Entry 1105 Genome Structure 1106 Translation and Proteolytic Processing 1107 Features of the Structural Proteins 1108 Features of the Nonstructural Proteins 1109 RNA Replication 1112 Membrane Reorganization and the Compartmentalization of Flavivirus Replication 1112 Assembly and Release of Particles from Flavivirus-infected Cells 1112 Host Resistance to Flavivirus Infection 1113

Genetic organization and diversity of the hepatitis C virus.

Abstract: The nucleotide sequence of the RNA genome of the human hepatitis C virus (HCV) has been determined from overlapping cDNA clones. The sequence (9379 nucleotides) has a single large open reading frame that could encode a viral polyprotein precursor of 3011 amino acids. While there as little overall amino acid and nucleotide sequence homology with other viruses, the 5' HCV nucleotide sequence upstream of this large open reading frame has substantial similarity to the 5' termini of pestiviral genomes. The polyprotein also has significant sequence similarity to helicases encoded by animal pestiviruses, plant potyviruses, and human flaviviruses, and it contains sequence motifs widely conserved among viral replicases and trypsin-like proteases. A basic, presumed nucleocapsid domain is located at the N terminus upstream of a region containing numerous potential N-linked glycosylation sites. These HCV domains are located in the same relative position as observed in the pestiviruses and flaviviruses and the hydrophobic profiles of all three viral polyproteins are similar. These combined data indicate that HCV is an unusual virus that is most related to the pestiviruses. Significant genome diversity is apparent within the putative 5' structural gene region of different HCV isolates, suggesting the presence of closely related but distinct viral genotypes.

The molecular biology of coronaviruses.

Abstract: Coronaviruses are large, enveloped RNA viruses of both medical and veterinary importance. Interest in this viral family has intensified in the past few years as a result of the identification of a newly emerged coronavirus as the causative agent of severe acute respiratory syndrome (SARS). At the molecular level, coronaviruses employ a variety of unusual strategies to accomplish a complex program of gene expression. Coronavirus replication entails ribosome frameshifting during genome translation, the synthesis of both genomic and multiple subgenomic RNA species, and the assembly of progeny virions by a pathway that is unique among enveloped RNA viruses. Progress in the investigation of these processes has been enhanced by the development of reverse genetic systems, an advance that was heretofore obstructed by the enormous size of the coronavirus genome. This review summarizes both classical and contemporary discoveries in the study of the molecular biology of these infectious agents, with particular emphasis on the nature and recognition of viral receptors, viral RNA synthesis, and the molecular interactions governing virion assembly.

Classification and Nomenclature of Viruses

Abstract: The results of the meetings of the International Committee on Taxonomy of Viruses, held in Madrid, September 1975, are briefly reported: rules of viral nomenclature, composition of the new Executive Committee, and a list of the names so far officially agreed. Introduction The International Committee on the Taxonomy of Viruses (ICTV), which is a committee of the Section on Virology of the International Association of Microbiological Societies (IAMS), completed a round of meetings during the Third International Congress for Virology that was held in Madrid from September 10--17, 1975. Since ICTV only meets during these conferences, which are held every four years, the meetings are important occasions for reviewing the classification and nomenclature of viruses. Decisions on new names, which encapsulate the recognition of natural "groups" of viruses, evolve slowly. Official approval for new names depends upon a series of sequential steps ; recommendations by one or more of the subcommittees of the Executive Committee of ICTV (subcommittees on Bacterial, Invertebrate, Plant and Vertebrate Viruses respectively, and for some of the larger viral groups which span several kinds of hos t s the Coordination Subcommittee), which are considered by the Executive Committee of ICTV and may finally be submitted for approval by ICTV itself. Only after this final approval does a name become "official". The results of the last five years of work by ICTV and its committees will be published early this year as a separate volume of "Intervirology", the official journal of the Section on Virology of IAMS, and additional copies will be produced for sale as separates. This "Second P~eport" will include, besides "approved" and common names of virus groups, a brief description of the properties of each