Infectious Disorders - Drug Targets - Volume 21, Issue 7, 2021

A successful viral infection is due to the effective evasion of viruses of the immune system. The entry of viruses is usually detected by different cellular receptors including PRRs. Recognition of the viral genome leads to the production of interferons through a signaling stream. This review article provides brief information regarding escape mechanisms of DNA and RNA viruses from the host immune system. These strategies include viral endonuclease activity, cap snatching of host mRNA, the formation of replication organelles, stress granule formation, membrane modifications, action of proteases, and evasion from ISGs. Moreover, the strategies of DNA viruses to inhibit immune responses include subversion of mRNA, transcriptional factors, adaptor proteins, PRRs, evasion from T lymphocytes, genomic diversity, theft or seizure of host defense proteins, imitation of host factors like affecting cytokines and chemokines of the host, suppression or inhibition of apoptosis, and proteasomal degradation of host antiviral proteins by DNA viruses. The knowledge of these mechanisms is pivotal to understanding different methodologies that viruses have created to escape antiviral cellular reactions of the host as well as virus-host interactions and the origin of viral pathogenesis. Also, this knowledge is significant for the design of gene targeting vectors, antiviral vaccines, and the development of effective treatments directed against DNA and RNA viruses.

A novel coronavirus, SARS- CoV-2 (2019-nCoV), emerged in December 2019 as an immediate global challenge. Comprehensive efforts at the present time are focused simultaneously on containing the spread of this virus and extenuating the ill effects. There is an immediate need for drugs that can help before a vaccine can be developed. Researchers are endeavoring to find antiviral therapies specific to the virus. As the condition is an emerging, rapidly evolving situation and development of new drugs is a long process, and is unfeasible to face the immediate global challenge. Strategy to reposition the previously used drugs can prove to be effective to combat this difficult to treat pandemic. Several drugs such as Hydroxychloroquine, Umifenovir, Remdesivir, Lopinavir/ Ritonavir, interferon, Darunavir, Favipiravir, Nitazoxanide, etc. are currently undergoing clinical studies to test the safety and efficacy of the drug against this pandemic. The present review gives a snapshot look at the current clinical experience with repurposed antiviral drugs.

The Covid-19 pandemic has become a major challenge for health care professionals and researchers all over the world. The discovery and development of new drugs require time for passing the quality, safety, and efficacy criteria. Hence the only available option is to rely on herbal or natural remedies as well as other existing ones. Nature has its healing power and has the remedy for all the ailments from which life on earth is struggling. For this pandemic situation also, nature should have created a remedy but finding a loophole is in the hands of our researchers. In this hypothesis, a novel combination strategy is introduced with the existing drugs such as hydroxychloroquine and flavonoid in a volatile liquid-based Nanoformulation incorporated into an inhaler as a possible remedy for the management of coronavirus infection. The synergistic activity of this combination shall pave the way for an effective therapeutic strategy for the treatment of COVID-19 symptoms.

Recently, novel coronavirus infection (COVID-19) emerged in Wuhan, China has been declared as pandemic by WHO. Until now, no evidence is documented regarding its wild animal reservoir or intermediary host, but, human-to-human transmission, asymptomatic carriers were very much observed. The number of confirmed cases and death toll have been increased almost all over the world indicating its potential threat to public health. Though the phylogenetic analysis shows some similarity of SARS-CoV2 to bat betacoronaviruses, it exhibited significant variation in S1 domain of spike protein from bat-derived viruses. S1 domain plays an important role in receptor binding and it can be a target for the development of therapeutics and vaccines. In this review, we have discussed the updates on transmission, diagnosis, genome analysis and comparison, treatment options and clinical trials of COVID-19.

Background: Coronavirus disease 2019 (COVID-19) is a life intimidating viral infection caused by a positive sense RNA virus belonging to the Coronaviridae family, named severe acute respiratory distress syndrome coronavirus 2 (SARA-CoV-2). Since its outbreak in December 2019, the pandemic has spread to more than 200 countries, infected more than 26 million, and claimed the lives of more than 800,000 people. As a disease, COVID-19 can lead to severe and occasionally fatal respiratory problems in humans. Infection with this virus is associated with fever, cough, dyspnea, and muscle aches, and it may progress to pneumonia, multiple organ failure, and death. To date, there is no specific antiviral treatment against this virus. However, the main viral protease has been recently discovered and it is regarded as an appropriate target for antiviral agents in the search for the treatment of COVID-19, due to its pivotal role in polyproteins processing during viral replication. Aim: Consequently, this study intends to evaluate the effectiveness of FDA-approved anti-viral drugs against SARA-CoV-2 through a molecular docking study. Methods: AutoDock Vina in PyRx platform was used for docking analysis against the main viral protease (Mpro) (PDB ID 6LU7), and Computed Atlas of Surface Topography of proteins (CASTp 3.0) was applied for detecting and characterizing cavities, pockets, and channels of this protein structure. Results: Results revealed that among the conventional antiviral drugs, the protease inhibitors, lopinavir, amprenavir, indinavir, maraviroc, saquinavir, and daclatasvir showed high binding affinity and interacted with amino acid residues of the binding site. Conclusion: In conclusion, protease inhibitors may be effective potential antiviral agents against Mpro to combat SARS-CoV-2.

Background: H1N1 is known to cause periodic seasonal flu in the Indian subcontinent since 2009. The clinical course and the underlying immunity of the host contribute to the development of secondary bacterial infections in the infected patients. Objectives: This study aims to analyze the secondary bacterial infections in confirmed H1N1 cases admitted in our hospital (from 2015 to 2018) with respect to the comorbidities, complications, associated bacteria with its antibiotic susceptibility pattern, and the outcome of such episodes. Material and Methods: Data of 164 patients admitted in a tertiary care hospital with H1N1 was extracted from medical records using a semi-structured case report form. Data were entered and analyzed with SPSS version 17. A p-value of <0.05 was considered statistically significant. Results: Most patients were aged above 40 years with female preponderance. In our study, 42% of patients had comorbidities. Only 14 (8.53%) had secondary bacterial infection confirmed by culture. Klebsiella pneumoniae and Acinetobacter baumannii were the most common bacteria that were isolated. They were treated based on the culture reports. There was no mortality in patients with a secondary bacterial infection. Conclusion: The early start of the antiviral agents and adherence to the antibiotic policy of the hospital contributed to lower secondary bacterial infections and zero mortality.

Background: Helicobacter pylori infection is identified as a major cause of stomach ulcers, chronic inflammation and gastric cancer in hemodialysis patients. Dialysis also leads to changes in the composition and flow of saliva. Objective: The aim of this study was to investigate the salivary Helicobacter pylori infection, Calcium, Urea, pH and flow rate in hemodialysis patients in comparison to the healthy control group. Methods: In this study 48 hemodialysis patients and 48 healthy subjects were compared. The prevalence of Helicobacter pylori infection was determined by PCR method. Calcium, Urea, pH, salivary flow and gastrointestinal complications in both groups were measured and compared. Results: Prevalence of Helicobacter pylori was 12.48 (25.0%) in the study group and 2.48 (4.2%) in the controls (P=0.000). Urea, calcium and pH were significantly higher in the patient group. The mean salivary flow rate decreased significantly in the patient group. 58.3% of patients group had gastrointestinal complications. Conclusion: Oral cavity as an important external source of Helicobacter pylori may play an important role in gastrointestinal problems of hemodialysis patients. Helicobacter pylori, Urea, calcium and pH were significantly higher in the patient group. Chronic renal failure can increase pH, urea and calcium in saliva and decrease salivary flow rate.

Background: Antibiotics are known to be effective in treating bacterial infectious disease. Changes in microflora and mucosal dysbiosis may take place after antibiotic treatment. We investigated in this research the effect of anti-Helicobacter pylori treatment (AHT) on local immunity of the female genital tract. Methods: The study identified the levels of cytokines IL-8 and TNF-α in vaginal secretion in a group of female patients with Helicobacter-associated acid-related diseases who were or were not treated with antibiotics against Helicobacter Pylori. Results: Research outcomes turned out that the secretory cytokine (chemokine) IL-8 is dramatically increased in the vaginal mucosa in patients treated with antibiotics, specifically in post-menopause women. Conclusion: Helicobacter pylori eradication treatment affects the immune status of the female genital tract.

Background: Serratia spp. is a common enteric bacterium generally thought not to be pathogenic in the gastrointestinal tract. Serratia marcescens is a member of the genus Serratia, which is a part of the family Enterobacteriales. Of all Serratia species, S. marcescens is the most common clinical isolate and the most important human pathogen. Objective: We discuss here four cases of Serratia marcescens which were reported in our laboratory at the Department of Microbiology Government Medical College and Hospital Chandigarh within six months of duration. Method: All the samples were processed and identified using standard microbiological techniques. The isolates of Serratia marcescens were identified, depending upon their biochemical and morphological characteristics, and further confirmed by MALDI-TOF-MS, PGIMER Chandigarh. Result: In one of the four cases, polymicrobial infection was observed, and among the cases, one patient was diabetic and the rest three patients were immunocompetent. The importance of detection of Serratia marcescens is related to the concern regarding its increased spread in hospital settings as nosocomial infection. Conclusion: We need to identify and isolate this pathogen not thinking of it only as a contaminant and opportunistic pathogen but as a pathogen which can lead to serious infections in hospital settings.

Background: Staphylococcus haemolyticus is one of the most frequently coagulasenegative staphylococci isolated from healthcare-associated infections, mainly those related to implanted medical devices. Objectives: This study aimed to determine the antimicrobial susceptibility profile and biofilm forming capacity of S. haemolyticus isolated from bloodstream infections. Methods: A total of 40 S. haemolyticus isolates were characterized according to their genetic relatedness by repetitive element sequence based-PCR (REP-PCR), antimicrobial susceptibility profile, SCCmec typing, ability to form biofilm on abiotic surface and occurrence of putative genes related to biofilm formation. Results: One S. haemolyticus was susceptible to all antimicrobials. The other isolates (n=39) were resistant to cefoxitin; and among them 34 (87.2%) harbored the mecA gene into the SCCmec type I (5.9%), type III (29.4%), type IV (5.9%) and type V (20.6%); and 38.2% isolates were designated as NT. Apart from cefoxitin, 94.9% of the isolates were resistant to at least four antimicrobial classes, and 32.5% displayed minimal inhibitory concentration (MIC) values higher than 4.0 μg/mL for vancomycin. All isolates formed biofilm on polystyrene surface and were classified as strong biofilm-producers, except for one isolate. All isolates were negative for icaA gene, and the prevalence of the other genes was as follows: atl, 100%; fbp, 92.5%; aap, 90.0%; and bap, 20.0%. Conclusion: This study reports a high prevalence of methicillin-resistant S. haemolyticus displaying decreased susceptibility to vancomycin with the ability to form strong biofilms on abiotic surface. The results support the importance of controlling the adequate use of antimicrobials for the treatment of staphylococcal infections.

Background: West Nile virus (WNV) is a positive-sense single-stranded RNA virus of the family Flaviviridae and genus Flavivirus. The virus is transmitted primarily by the bite of Culex species mosquito and is of global concern. The infection is associated with a wide spectrum of signs and symptoms and is more fatal in the elderly, infants, and immunocompromised individuals. Case Presentation: We report a case of WNV meningoencephalitis in an immunocompetent female who presented with features of acute meningitis with a 5-days history. After the radiological suspicion of viral meningoencephalitis, viral serology was performed and was reactive for IgM antibody against WNV, delaying the diagnosis for at least 5 days. Conclusion: The purpose of this case report is to prime the treating physicians on the usefulness of viral serology in such a scenario. Viral serology is a simple and relatively rapid technique to diagnose or rule out the suspected viral cause of meningoencephalitis and minimize the time gap between diagnosis and start of supporting treatment wherever appropriate antivirals are not available for clinical use.

Background: Since December 2019, there has been an increasing number of patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world. As of March 2020, the World Health Organization declared a global pandemic. Case Presentation: To our best knowledge, this is the first report of a patient with SARS-CoV-2 infection presenting with constrictive pericarditis, possibly from the COVID infection. She was presented after a week of fever, persistent dry cough, and diarrhea. She received a single dose of hydroxychloroquine 400 mg, Oseltamivir 75 mg every 12 hours, lopinavir/ritonavir (Kaletra) 400/100 mg every 12 hours, and levofloxacin 750 mg daily. After 24 hours, she was immediately transferred to the Intensive Care Unit (ICU) because of dyspnea and progressive respiratory failure with a drop of the O2 saturation to 70%. Conclusion: After a week of progress, her respiratory condition deteriorated again. She was re-admitted to the ICU and she expired. She died due to constrictive pericarditis, most probably caused by SARS-CoV-2.