Influenza with a tendency to cause pandemic and epidemic is an infectious disease with a high of morbidity and mortality. Neuraminidase (NA) inhibitors are proved to prevent and treat influenza. Among the four Neuraminidase inhibitors (NAIs) licensed, oseltamivir is most commonly used. With the extensive usage, several variants containing mutant NAs especially H274Y point mutation exhibit reduced susceptibility. In this review, we covered the current drugs available for influenza, the analysis of active site of NA, the mutant types of NAs and the molecular mechanism of drug resistance brought by H274Y mutant NAs. For recovering the susceptibility to oseltamivir, many series of oseltamivir analogues were designed. We present the details of the strategies of strengthening the interactions with S2 via introducing strong basic fragment, targeting additional subpockets and making full use of Zone X by modifying 3-pentyl of OC. PROTAC targeting NA and combination therapies are also introduced. Further, the advantages and disadvantages of these methods are also discussed.

Viral infections have a great impact on human health. The urgent need to find a cure against different viruses led us to investigations in a vast range of drugs. Azithromycin (AZT), classified as a macrolide, showed various effects on different known viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV), Zika, Ebola, Enterovirus (EVs) and Rhinoviruses (RVs), and Influenza A previously; namely, these viruses, which caused global concerns, are considered as targets for AZT different actions. Due to AZT background in the treatment of known viral infections mentioned above (which is described in this study), in the early stages of COVID-19 (a new zoonotic disease caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) development, AZT drew attention to itself due to its antiviral and immunomodulatory effects as a valuable candidate for COVID-19 treatment. AZT usage instructions for treating different viral infections have always been under observation, and COVID-19 is no exception. There are still debates about the use of AZT in COVID-19 treatment. However, eventually, novel researches convinced WHO to announce the discontinuation of AZT use (alone or in combination with hydroxychloroquine) in treating SARS-CoV-2 infection. This research aims to study the structure of all of the viruses mentioned above and the molecular and clinical effects of AZT against the virus.

Coronavirus disease 2019 (COVID-19) occurs in the influenza season and has become a global pandemic. The present study aimed to examine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infection with influenza A virus (IAV) in an attempt to provide clues for the antiviral interventions of co-infected patients. We described two patients who were co-infected with SARS-CoV-2 and IAV treated at Wuhan Union Hospital, China. In addition, we performed a review in PubMed, Web of Science and CNKI (from January 1 up to November 1, 2020) with combinations of the following key words: \"COVID-19, SARS-COV-2, influenza A and co-infection\". A total of 28 co-infected patients were enrolled in the analysis. Of the 28 patients, the median age was 54.5 years (IQR, 34.25-67.5) and 14 cases (50.0%) were classified as severe types. The most common symptoms were fever (85.71%), cough (82.14%) and dyspnea (60.71%). Sixteen patients had lymphocytopenia on admission and 23 patients exhibited abnormal radiological changes. The median time from symptom onset to hospital admission was 4 days (IQR, 3-6), and the median time of hospital stay was 14 days (IQR, 8.5-16.75). In conclusion, patients with SARS-COV-2 and IAV co-infection were similar to those infected with SARS-COV-2 alone in symptoms and radiological images. SARS-COV-2 co-infection with IAV could lead to more severe clinical condition but did not experience longer hospital stay compared with patients infected with SARS-COV-2 alone.

The influenza virus is classified into four types A, B, C, and D, but type A and B are responsible for major illnesses in people with influenza A being the only virus responsible for flu pandemics due to the presence of two surface proteins called hemagglutinin (H) and neuraminidase (N) on the virus. The two subtypes of influenza A virus, H1N1 and H3N2, have been known to cause many flu pandemics. Both subtypes change genetically and antigenically to produce variants (clades and subclades, also know as groups and subgroups). H3N2 tends to change rapidly, both genetically and antigenically whereas that of H1N1 generally tends to have smaller changes. Influenza A (H3N2) viruses have evolved to form many separate, genetically different clades that continue to co-circulate. Influenza A(H3N2) viruses have caused significant deaths as per WHO report. The review describes methods for detection of influenza A(H3N2) viruses by conventional serological methods as well as the advanced methods of molecular biology and biosensors. All these methods are based on different parameters and have different targets but the goal is to improve specificity and increase sensitivity. Amongst the molecular methods, real-time polymerase chain reaction (RT-PCR) is considered a gold standard test due to its many advantages whereas a number of other molecular methods are time-consuming, complex to perform or lack specificity. The review also considers bio-sensing methods for simple, rapid, highly sensitive, and specific detection of H3N2. The classification and principle of various H3N2 biosensors are also discussed.

Neuraminidase inhibitors (NAIs), that currently include oseltamivir (Tamiflu® ), zanamivir (Relenza® ), peramivir (Rapivab® ) and laninamivir (Inavir® ), constitute an important class of antivirals recommended against seasonal influenza A and B infections. NAIs target the surface NA protein whose sialidase activity is responsible for virion release from infected cells. Because of their pivotal role in the transcription/translation process, the polymerase acidic (PA) and polymerase basic 1 and 2 (PB1 and PB2, respectively) internal proteins also constitute targets of interest for the development of additional anti-influenza agents. Baloxavir marboxil (BXM), an inhibitor of the cap-dependent endonuclease activity of the influenza PA protein, was approved in the United States and Japan in 2018. Baloxavir acid (BXA), the active compound of BXM, demonstrated a potent in vitro activity against different types/subtypes of influenza viruses including seasonal influenza A/B strains as well as avian influenza A viruses with a pandemic potential. A single oral dose of BXM provided virological and clinical benefits that were respectively superior or equal to those displayed by the standard (5 days, twice daily) oseltamivir regimen. Nevertheless, BXM-resistant variants have emerged at relatively high rates in BXM-treated children and adults. Consequently, there is a need to study the fitness (virulence and transmissibility) characteristics of mutants with a high potential to emerge as such variants can compromise the clinical usefulness of BXM. The purpose of this manuscript is to review the fitness properties of influenza A and B isolates harbouring mutations of reduced susceptibility to BXA.

A case of acute respiratory distress syndrome due to SARS-CoV-2 and Influenza A co-infection and a mini-review of the literature is reported. Even in COVID-19 epidemics, the early identification of concurrent respiratory pathogens is important to improve etiological diagnosis, preventive measures and patients\' clinical management and outcome.

In spring 2013, a novel avian-origin influenza A (H7N9) virus emerged in mainland China. The burden of H7N9 infection was estimated based on systematic review and meta-analysis. The systematic search for available literature was conducted using Chinese and English databases. We calculated the pooled seroprevalence of H7N9 infection and its 95% confidence interval by using Freeman-Tukey double arcsine transformation. Out of 16 890 records found using Chinese and English databases, 54 articles were included in the meta-analysis. These included studies of a total of 64 107 individuals. The pooled seroprevalence of H7N9 infection among humans was 0.122% (95% CI: 0.023, 0.275). In high-risk populations, the highest pooled seroprevalence was observed among close contacts (1.075%, 95% CI: 0.000, 4.357). The seroprevalence among general population was (0.077%, 95% CI: 0.011, 0.180). Our study discovered that asymptomatic infection of H7N9 virus did occur, even if the seroprevalence among humans was low.

UNASSIGNED: There is limited evidence of studying the associated factors of acute kidney injury (AKI) among patients with influenza A (H1N1) virus infection pandemic in 2009. AKI is one of the most prevalent complications in the intensive care unit. Its incidence is associated with high mortality and negative impacts on long-term survival. The aim of this narrative review was to determine the prevalence and mortality due to AKI, among patients admitted with the H1N1 virus.
UNASSIGNED: A narrative review of studies reporting about treatment measures and mortality associated with AKI during the H1N1 pandemic over a 10-year period (from September 2009 to August 2018), was performed. We searched the following databases; EMBASE, Medline/PubMed, NHS evidence, Google Scholar, and the Cochrane Library. Our inclusion revealed 20 studies of patients (n = 3579) who were admitted with H1N1 infection and developed AKI.
UNASSIGNED: In this study, 33% of patients (n = 1164) who were admitted with H1N1 infection had developed AKI. Within the first 5 years (2009 to 2013), 36% of patients (n = 1013) developed AKI. Within the next 5 years (2014-2018), 812 patients were admitted with the H1N1 infection and 18% of patients (n = 150) had developed AKI. Over the 10 years, there was a 50% reduction in the number of patients who developed AKI (2009 and 2018) (P < 0.0001).
UNASSIGNED: Patients showed varied responses to treatment measures, depending on their geographical location, comorbidities, and other characteristics. Despite a reasonable prevalence of AKI among patients with the H1N1 virus infection, the mortality over the last 10 years was reduced, with renal replacement therapy as a common therapy in most studies.

It is quite intriguing that bovines were largely unaffected by influenza A, even though most of the domesticated and wild animals/birds at the human-animal interface succumbed to infection over the past few decades. Influenza A occurs on a very infrequent basis in bovine species and hence bovines were not considered to be susceptible hosts for influenza until the emergence of influenza D. This review describes a multifaceted chronological review of literature on influenza in cattle which comprises mainly of the natural infections/outbreaks, experimental studies, and pathological and seroepidemiological aspects of influenza A that have occurred in the past. The review also sheds light on the bovine models used in vitro and in vivo for influenza-related studies over recent years. Despite a few natural cases in the mid-twentieth century and seroprevalence of human, swine, and avian influenza viruses in bovines, the evolution and host adaptation of influenza A virus (IAV) in this species suffered a serious hindrance until the novel influenza D virus (IDV) emerged recently in cattle across the world. Supposedly, certain bovine host factors, particularly some serum components and secretory proteins, were reported to have anti-influenza properties, which could be an attributing factor for the resilient nature of bovines to IAV. Further studies are needed to identify the host-specific factors contributing to the differential pathogenetic mechanisms and disease progression of IAV in bovines compared to other susceptible mammalian hosts.

Among scientists, there exist mixed opinions whether equine influenza viruses infect man. In this report, we summarize a 2016 systematic and comprehensive review of the English, Chinese, and Mongolian scientific literature regarding evidence for equine influenza virus infections in man. Searches of PubMed, Web of Knowledge, ProQuest, CNKI, Chongqing VIP Database, Wanfang Data and MongolMed yielded 2831 articles, of which 16 met the inclusion criteria for this review. Considering these 16 publications, there was considerable experimental and observational evidence that at least H3N8 equine influenza viruses have occasionally infected man. In this review we summarize the most salient scientific reports.