Drug discovery and development against coronavirus disease 2019 (COVID-19) is the utmost need and the most challenging task of the hour. Many research groups from different countries are working continuously in this direction, and till 8 March 2020, a total of 382 clinical trials have been registered on the WHO’s International Clinical Trials Registry Platform [1]. There is an urgent need to identify specific targets to design promising therapeutic agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. Analysis of SARS-CoV-2 reveals seven major target proteins that can be considered for drug design against the virus. These include the spike, envelope, membrane, nucleocapsid, protease, hemagglutinin esterase and helicase [2, 3]. Beyond these, several Non Structural Proteins (NSPs) can also be evaluated as targets for drug development [4]. There are only a few Protein Data Bank (PDB) Ids available related to SARS-CoV-2 in the RCSB database. Table 1 summarizes recently released PDB Ids (from 5.2.2020 to 25.3.2020) for various SARS-CoV-2 targets [5].
The host range of a virus is defined as the number of species a virus potentially infects. The specialist virus infects one or few related species while the generalist virus infects several different species, possibly in different families. Origin of generalist viruses from their specialist nature and the expansion of the host range of the generalist virus occur with the host shift event in which the virus encounters and adapts to a new host. Host shift events have resulted in the majority of the newly emerging viral diseases. This review discusses the advantages and disadvantages of generalist over specialist viruses and the unique features of plant viruses and their hosts that result in a higher incidence of generalist viruses in plants.
Although there is continuous work in progress in some of the above mentioned approaches, but there is still no drug/vaccine available to treat COVID-19 Drug repurposing offers an economical and rapid strategy to discover a potential therapeutic agent in the current hectic situation This compilation may be helpful to the researchers, drug developers and health agencies to look into the matter and work against the possible targets to develop a therapeutic candidate against COVID-19 The challenge associated with drug repurposing is the inadequate efficacy of single therapeutic candidate Another complication associated with this approach is to search and analyze the huge amount of previously reported data to make efficient and effective use against a new indication The complex/unclear events of the pathophysiology of SARS-CoV-2 also offer a great challenge to select a candidate for repurposing
Introduction: The common cold syndrome of acute upper respiratory tract viral infection is the most common disease among mankind and is an extremely common illness in children. There is a great need for a safe and effective antiviral treatment with minimal side effects. The challenge in developing a treatment is the numerous and varied respiratory viruses that cause this common illness and the need for a treatment with good tolerability and safety. Explanation: All respiratory viruses must reach the cell surface by passing through respiratory fluid and mucus, and this common feature may allow for the development of antivirals that capture viruses during this transit. This article discusses how large polyanionic molecules such as iota-carrageenan may trap positively charged respiratory viruses. Iota-carrageenan is a large polysaccharide molecule which is neither absorbed from the respiratory tract nor metabolised. It, therefore, does not have any pharmacological properties. Iota-carrageenan nasal spray has been shown to reduce the titres of respiratory viruses and to reduce the severity of symptoms in placebo-controlled clinical trials, including children and adults. The results of four clinical trials are presented. Conclusion: Iota-carrageenan is a good candidate as a safe and effective non-specific antiviral treatment for common cold, and more research is justified on polyanionic molecules like carrageenans as antivirals.
Evolutionary biology has become one of the imperative determinants explaining the origin of several viruses which were either identified decades back or are recognized lately using metagenomic approaches. Several notifiable emerging viruses like influenza, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), Ebola, Hendra, Nipah and Zika viruses have become the leading causes of epidemics and losses thereto in both human and animals. The sufferings are higher due to gastroenteritis causing viruses including Astrovirus, Calicivirus, Enterovirus, Kobuvirus Picobirnavirus, Sapelovirus, Teschovirus, and many more. Notably, the majority of the emerging viruses enclose RNA genome and these are more prone for insertions/mutation in their genome, leading to evolving viral variants. Rapidity in viral evolution becomes a big hitch in the development process of successful vaccines or antiviral. The prominent gastroenteric virus is rotavirus, which is a double-stranded RNA virus with a segmented nature of genome enabling higher reassortment events and generates unusual strains with unique genomic constellations derivative of parental rotavirus strains. Although most rotaviruses appear to be host restricted, the interspecies transmission of rotaviruses has been well documented across the globe. The nocturnal bats have been accepted harbouring many pathogenic viruses and serving as natural reservoirs. Indications are that bats can also harbour rotaviruses, and help in virus spread. The zooanthroponotic and anthropozoonotic potential of rotaviruses has significant implications for rotavirus epidemiology. Hitherto reports confirm infection of humans through rotaviruses of animal origin, exclusively via direct transmission or through gene reassortments between animal and human strain of rotaviruses. There is a need to understand the ecology and evolutionary biology of emerging rotavirus strains to design effective control programs.
Introduction: Throughout the past few years, Pepino Mosaic Virus (PepMV) has rapidly evolved from an emerging virus to endemic pathogen that causes significant losses in tomato crops worldwide. Reliable detection and molecular characterization are very important tools to support disease control. Cross-protection can also be an effective strategy, but the efficacy depends strongly on the genotype. The genetic composition of the PepMV population in Morocco has not yet been determined. Aims: The current study aims to genetically characterize twelve PepMV isolates (PepMV-MA), all from different Moroccan tomato production areas, by analyzing nucleotide sequences of a part of the RNA-dependent RNA polymerase (RdRp), Triple Gene Block (TGB) and Coat Protein (CP) genes. Results: The sequence analysis of the twelve PepMV-MA isolates shows minor nucleotide differences between them, which implies a homogenous population. The phylogenetic analysis, based on the comparison with the major genotypes, showed that Moroccan PepMV populations share a very high sequence identity, 98%, with the Chilean strain (CH2), while the shared identity with the European strains (EU) is only 85%. Interestingly, Moroccan isolates reveal specific single nucleotide polymorphisms, some of which lead to amino acids changes. These mutations have never been described before, suggesting distinct variants that may enhance aggressiveness and symptomatology. Conclusion: Our careful sequence analysis and genotype determination, which placing homogenous Moroccan PepMV strains into CH2 genotype, would be a prerequisite for deploying effective cross-protection strategies for controlling the pathogen in the field.
Background: BK virus, which is associated with Prostate Cancer (PCa), have a global seroprevalence in humans. Based on the sequences of VP1 and the Large Antigen (LTAg) genes, there are four subtypes of BKV. Each subtype has its own subgroups. Objective: The aim of this study was to identify the BKV subtype that circulates among Sudanese patients with PCa. Materials and Methods: A total of 8 samples from our previous work on BKV were studied in this investigation. The LTAg gene was partially amplified (176nt) by a homemade PCR. All the amplicons were purified and subjected to sequencing. Bioedit version 7.0 and Mega X version 6.0 were used to analyze the sequence and compare the results with the BKV sequences and build a phylogenetic tree. Results: All the BKV LTAg gene sequences derived from Sudanese patients were classified with Subtype-1 BKV strains from Iran and Japan. Translated protein alignment showed that some isolates had identical amino acids with Iranian and Japanese strains, whereas others had a silent mutation. Interestingly, a point mutation was identified in the sequences of isolate 5 and 8 where adenine nucleotide (A) was replaced with Cytosine (C) at position 276, resulting in amino acid substitution. Conclusion: It was concluded that all the BKV isolates which circulated among Sudanese prostate tumor patients belonged to subtype 1. These findings only highlighted the need for the molecular detection and subtyping of BKV strains in Sudanese patients in order to better demonstrate the relationship between BKV infection and PCa.
Background:Female Sex Workers (FSW) have increased vulnerability to viral hepatitis B, C and D transmission. Our study aimed to assess the seroprevalence of hepatitis B, C and D viruses and their associated factors among FSW in Ouagadougou, Burkina Faso.Methods:This is a cross-sectional study among FSW at least 18 years old in Ouagadougou, Burkina Faso. Data were collected from February 2013 to May 2013 using Respondent-Driven Sampling (RDS). Hepatitis B, C, and D tests were performed on FSW storage serums using fourth generation ELISA kits. Survey-weighted bivariate and multivariate logistic regression analyses were performed using Stata version 14 to identify factors associated with viral hepatitis infections.Results:Population-weighted prevalence of viral hepatitis infections in FSW was respectively 18.2% (95%CI: 14.4-22.9) for Hepatitis B Virus (HBV), 10.6% (95%CI: 07.5-14.8) for Hepatitis C Virus (HCV) and 1.5% (95Cl: 0.2-10.3) for Hepatitis D Virus (HDV). Factors independently associated with HCV include positive HIV status, inconsistent condom use during the last 12 months, condom reuse with clients, sex with clients in the street, bars or public gardens. No sociodemographic or behavioral factors were independently associated with HBV infection.Conclusion:The prevalence of HBV and HCV was high among FSW and the prevalence of HDV was relatively low in this group in Burkina Faso. These findings suggest urgent and comprehensive prevention of these viruses through education for safer sex and behaviors, and immunization against HBV for FSW.
Background: The impact of Enterovirus Real Time-Polymerase Chain Reaction assay (EV RT-PCR) on hospitalization lengths of patients with aseptic meningitis has been investigated but the impact of early EV RT-PCR results released on time before patient discharge remains unclear during Echovirus meningitis outbreaks. Objective: To assess a potential correlation between EV RT-PCR turn-around time and hospitalization lengths during an Echovirus meningitis outbreak. Method: Eighteen patients demonstrating a positive EV RT-PCR assay performed on Cerebrospinal Fluid (CSF) samples collected between October 1 st 2014 and December 31st 2014 were retrospectively included. Viral protein 1 (VP1) gene region was amplified and sequenced using a classical Sanger sequencing reaction. Clinical data were retrospectively collected from patient’s records. Quantitative variables expressed as median values and ranges were compared using Mann Whitney U test. Correlations were performed using simple regression analysis. Results: Phylogenetic VP1 sequence analyses identified that the outbreak was related to an Echovirus 30 strain in 7 out of the 10 cases with available sequencing data. The three remaining sequences analyses evidenced Echovirus 14, 9 and 7 strains. Hospitalization length was statistically shorter in children without comorbidity (n=5) than in adult patients (n=10) or neonates and children with comorbidity (n=3) (p=0.003 and 0.01 respectively), whereas EV RT-PCR turnaround time was not statistically different between these groups. Correlation between hospitalization length and EV RT-PCR turnaround time was poor (R 2 =0.06), especially in adults (R 2 =0.01) Conclusion: Our data indicated that EV RT-PCR turnaround time was not correlated to hospitalization length during a short Echovirus meningitis outbreak.
INTRODUCTION:In recent years, the Chandipura virus (CHPV) has emerged as an encephalitic pathogen and found associated with a number of outbreaks in different parts of India. Children under 15 years of age are most susceptible to natural infection. CHPV is emerging as a significant encephalitis, causing virus in the Indian subcontinent. Severe outbreaks caused by the virus have been reported from several parts of India.EXPALANATION:In the recent past, the noticeable association of CHPV with pediatric sporadic encephalitis cases as well as a number of outbreaks in Andhra Pradesh (2004, 2005, 2007 and 2008), Gujarat in (2005, 2009-12) and Vidarbha region of Maharashtra (2007, 2009-12) have been documented. Prevalence and seasonal activity of the virus in these regions are established by NIV through outbreak investigations, sero-survey and diagnosis of the referred clinical specimens. Recently CHPV has been isolated from pools of sand flies collected during outbreak investigations in Vidarbha region of Maharashtra. Since its discovery from India and above-mentioned activity of CHPV, it was suspected to be restricted only to India.CONCLUSION:However, CHPV has also been isolated from human cases during 1971-72 in Nigeria, and hedgehogs (Atelerix spiculus) during entomological surveillance in Senegal, Africa (1990-96) and recently referred samples from Bhutan and Nepal and from wild toque macaques (Macaca sinica) at Polonnaruwa, Sri Lanka during 1993 suggest its circulation in many tropical countries. Based on the limited study on vector related report, it appears that sandflies may be the principle vector.
Since the unexpected discovery of picobirnaviruses (PBV) in 1988, they have been reported in many animals including mammals and birds, which comprises both terrestrial and marine species. Due to their divergent characteristics to other viral taxa they are classified into a new family Picobirnaviridae. Although their pathogenicity and role in causing diarrhea still remains a question since they have been discovered in symptomatic and asymptomatic cases both. Recent studies employing state-of-art molecular tools have described their presence in various clinical samples, like stool samples from different mammals and birds, respiratory tracts of pigs and humans, sewage water, different foods, etc. Furthermore, their epidemiological status from different parts of the world in different hosts has also increased. Due to their diverse host and irregular host pattern their role in causing diarrhea remains alien. The heterogeneity nature can be ascribed to segmented genome of PBV, which renders them prone to continuous reassortment. Studies have been hampered on PBVs due to their non-adaptability to cell culture system. Here, we describe the molecular epidemiological data on PBVs in India and discusses the overall status of surveillance studies carried out till date in India.
AIMS & SCOPE It has been widely established that several virus infections are strictly correlated to cancerogenesis and may induce, through their reactivation, severe damages during chemotherapy treatments. For example, the direct role that Hepatitis B virus (HBV), plays in the development of liver cancer is well known. Nevertheless, in other cases, as Hepatitis C virus (HCV) or Hepatitis Delta Virus (HDV) the direct role of viral replication in cancer progression is still controversial, especially in some areas, like Italy, where these infections are endemic. The aim of this project is to update the epidemiological status of the incidence of HCC in Europe and HCV and HDV infection , with special attention to the changes during the time of route of transmission, and also investigate the interaction between viral reactivations and tumors.
Introduction: In the absence of a vaccine, there is an urgent need for the identification of effective agents that prevent HIV transmission in uninfected individuals. Non-vaccine Biomedical Prevention (nBP) methods, such as topical or systemic pre-exposure prophylaxis (PrEP), are promising strategies to slow down the spread of AIDS. Methods: In this study, we investigated the microbicidal efficacy of the viral membrane-disrupting amphipathic SWLRDIWDWICEVLSDFK peptide called C5A. We chose the bone marrow/liver/thymus (BLT) humanized mouse model as vaginal and rectal HIV transmission models. Results: We found that the topical administration of C5A offers complete protection against vaginal and rectal HIV challenges in humanized mice. After demonstrating that C5A blocks genital HIV transmission in humanized mice, we examined the molecular requirements for its microbicidal property. We found that the removal of four amino acids on either end of C5A does not diminish its microbicidal efficacy. However, the removal of four amino acids at both the ends, abolishes its capacity to prevent vaginal or rectal HIV transmission, suggesting that the length of the peptide is a critical parameter for the microbicidal activity of C5A. Moreover, we demonstrated that the amphipathicity of the helical peptide as well as its hydrophobic surface represents key factors for the microbicidal activity of C5A in humanized mice. Conclusion: With its noncellular cytotoxic activity, its property of neutralizing both HSV and HIV, and its unique mechanism of action that disrupts the stability of the viral membrane, C5A represents an attractive multipurpose microbicidal candidate to be combined with other anti-HIV agents including antiretrovirals.
Background:The lack of a vaccine for Hepatitis C virus (HCV) places children at a high risk of contracting the infection. It becomes necessary to accurately diagnose this infection for proper treatment as well as identifying potential risk factors for effective management.Aim:This study was conceived to assess the test performance of the commonly used Immunochromatographic test (ICT) strip and identify the associated clinical manifestations and risk factors of HCV in children in Enugu Metropolis.Method:A cross-sectional study involving randomly selected 270 children below six years of age was conducted in Enugu Nigeria. The subjects were screened for anti-HCV by ICT and Enzyme-Linked Immunosorbent Assay (ELISA) and the demographic, signs and symptoms and risk factors were collected.Results:A total of 50 out of 270 children were positive for anti-HCV with a seropositivity of 18.5%. ICT strip had a very low sensitivity of 38.00% with an accuracy of 88.52% in detecting anti-HCV. The presence of dark urine was associated (p= 0.01) with HCV infection.Conclusion:A seroprevalence of 18.5% of Anti-HCV was found in children below six years old in Enugu metropolis and the performance of ICT in diagnosing HCV infection was poor compared to ELISA.
Introduction:Exosomes are extracellular vesicles that originate as intraluminal vesicles during the process of multivescular body formation. Exosomes mediate intercellular transfer of functional proteins, lipids, and RNAs. The investigation into the formation and role of exosomes in viral infections is still being elucidated. Exosomes and several viruses share similar structural and molecular characteristics.Explanation:It has been documented that viral hijacking exploits the exosomal pathway and mimics cellular protein trafficking. Exosomes released from virus-infected cells contain a variety of viral and host cellular factors that are able to modify recipient host cell responses. Recent studies have demonstrated that exosomes are crucial components in the pathogenesis of virus infection. Exosomes also allow the host to produce effective immunity against pathogens by activating antiviral mechanisms and transporting antiviral factors between adjacent cells.Conclusion:Given the ever-growing roles and importance of exosomes in both host and pathogen response, this review will address the impact role of exosome biogenesis and composition after DNA, RNA virus, on Retrovirus infections. This review also will also address how exosomes can be used as therapeutic agents as well as a vaccine vehicles.
In recent years, the Antimicrobial Resistance (AMR) or Multidrug Resistance (MDR) and viral infections have become serious health issues, globally. Finally, after decades of negligence, the AMR/MDR and viral infection issues have now captured a worldwide attention of the global leaders, public health community, legalization authorities, academia, research-based organizations, and medicinal sector of the modern world, alike. Aiming to resolve these issues, various methodological approaches have been exploited, in the past several years. Among them, biomaterials-based therapeutic hydrogels are of supreme interests for an enhanced and efficient delivery in the current biomedical sector. Depending on the regulatory authorities and practices, the antibiotics consumption was expedited than ever before driven by rising and increasing access, across the globe. Though the emergence of AMR/MDR in microorganisms and emergence/reemergence of viral infections are considered as a natural phenomenon, however, these concerning issues have been driven by those mentioned above faulty human behavior. In this context, many scientists, around the globe, are working at wider spectrum to resolve this problematic issue, efficiently. A proper understanding of biological mechanisms is essential to combat this global threat to the living beings. In this review, an effort has been made to highlight the potent features of materials based hydrogels possessing antimicrobial and antiviral potentialities. The information is also given on the potential research activities, and possible mechanisms of actions of hydrogels are discussed with a closeup look at the future recommendations.
Introduction: Japanese encephalitis (JE) is recently declared as a notifiable disease in India due to its expanding geographical distribution. The disease notification facilitates effective implementation of preventive measures and case management. Expalantion: JE is a vector-borne disease that can be prevented by vaccine administration. It is caused by Japanese encephalitis virus (JEV), belonging to family Flaviviridae . Amongst the known etiological viral encephalitis agents, it is one of the leading viral agents of acute encephalitis syndrome in many Asian countries where it is identified to cause substantial morbidity and mortality as well as disability. Globally, it is responsible for approximately 68,000 clinical cases every year. Conclusion: In the absence of antivirals, patients are given supportive treatment to relieve and stabilize. Amongst available control strategies; vector control is resource intensive while animal and human vaccination are the most effective tool against the disease. This review highlights recent progress focusing challenges with diagnosis and prophylactic interventions.
Introduction: Zoonotic diseases are the infectious diseases that can be transmitted to human beings and vice versa from animals either directly or indirectly. These diseases can be caused by a range of organisms including bacteria, parasites, viruses and fungi. Viral diseases are highly infectious and capable of causing pandemics as evidenced by outbreaks of diseases like Ebola, Middle East Respiratory Syndrome, West Nile, SARS-Corona, Nipah, Hendra, Avian influenza and Swine influenza. Expalantion: Many viruses affecting equines are also important human pathogens. Diseases like Eastern equine encephalitis (EEE), Western equine encephalitis (WEE), and Venezuelan-equine encephalitis (VEE) are highly infectious and can be disseminated as aerosols. A large number of horses and human cases of VEE with fatal encephalitis have continuously occurred in Venezuela and Colombia. Vesicular stomatitis (VS) is prevalent in horses in North America and has zoonotic potential causing encephalitis in children. Hendra virus (HeV) causes respiratory and neurological disease and death in man and horses. Since its first outbreak in 1994, 53 disease incidents have been reported in Australia. West Nile fever has spread to many newer territories across continents during recent years. It has been described in Africa, Europe, South Asia, Oceania and North America. Japanese encephalitis has expanded horizons from Asia to western Pacific region including the eastern Indonesian archipelago, Papua New Guinea and Australia. Rabies is rare in horses but still a public health concern being a fatal disease. Equine influenza is historically not known to affect humans but many scientists have mixed opinions. Equine viral diseases of zoonotic importance and their impact on animal and human health have been elaborated in this article. Conclusion: Equine viral diseases though restricted to certain geographical areas have huge impact on equine and human health. Diseases like West Nile fever, Hendra, VS, VEE, EEE, JE, Rabies have the potential for spread and ability to cause disease in human. Equine influenza is historically not known to affect humans but some experimental and observational evidence show that H3N8 influenza virus has infected man. Despite our pursuit of understanding the complexity of the vector-host-pathogen mediating disease transmission, it is not possible to make generalized predictions concerning the degree of impact of disease emergence. A targeted, multidisciplinary effort is required to understand the risk factors for zoonosis and apply the interventions necessary to control it.
Introduction: Newcastle Disease (ND), caused by Avian avulavirus 1 (AAvV 1, avulaviruses), is a notifiable disease throughout the world due to the economic impact on trading restrictions and its embargoes placed in endemic regions. The feral birds including aquatic/migratory birds and other wild birds may act as natural reservoir hosts of ND Viruses (NDVs) and may play a remarkable role in the spread of the virus in environment. In addition, other 19 avulaviruses namely: AAvV 2 to 20, have been potentially recognized from feral avian species. Expalantion: Many previous studies have investigated the field prevailing NDVs to adapt a wide range of susceptible host. Still the available data is not enough to declare the potential role of feral birds in transmission of the virus to poultry and/or other avian birds. In view of the latest evidence related to incidences of AAvVs in susceptible avian species, it is increasingly important to understand the potential of viruses to transmit within the domestic poultry and other avian hosts. Genomic and phylogenomic analysis of several investigations has shown the same (RK/RQRR↓F) motif cleavage site among NDV isolates with same genotypes from domestic poultry and other wild hosts. So, the insight of this, various semi-captive/free-ranging wild avian species could play a vital role in the dissemination of the virus, which is an important consideration to control the disease outbreaks. Insufficient data on AAvV 1 transmission from wild birds to poultry and vice versa is the main constraint to understand about its molecular biology and genomic potential to cause infection in all susceptible hosts. Conclusion: The current review details the pertinent features of several historical and contemporary aspects of NDVs and the vital role of feral birds in its molecular epidemiology and ecology.
