Assessment of influenza A (H1N1, H3N2) oseltamivir resistance during 2017-2019 in Iran.

Background and Objectives: Neuraminidase inhibitors (NAIs) as an imperative antiviral for influenza prophylaxis and treatment are being consumed worldwide. Increasing use of these antivirals might be associated with drug resistance. Regarding the significance of these variations, this study aimed to investigate the mutations occurring in the NA gene of influenza A viruses leading to oseltamivir resistance during 2017-2019 in Iran. Materials and Methods: In this cross-sectional study, 40 influenza A (H1N1, H3N2) strains, isolated in National Influenza Center (NIC) from patients with Severe Acute Respiratory Infection (SARI) during 2017-2019 were subjected to RT-PCR and sequencing of NA complete gene. The frequency of oseltamivir resistance and variation of NA amino acids in these strains were investigated. Results: No significant mutation conferring oseltamivir resistance was detected. However, NA antigenic sites in these strains depicted minor changes compared to the vaccine strains. Among H3N2 isolates, mutations at 329, 344, 346 and 385 and among H1N1 isolates mutations at 143 and 188 residues occurred in NA antigenic regions. Conclusion: Evaluation of NA gene sequences, showed no resistant viruses to oseltamivir. Given that the viruses in the present study were the last viruses circulating in Iran before COVID-19 pandemic, the results will be beneficial to have a worthy comparison with the strains circulating after the pandemic. Constant monitoring for the emergence of drug-resistant variants and antigenic changes are crucial for all countries.

Lidocaine inhibits influenza a virus replication by up-regulating IFNα4 via TBK1-IRF7 and JNK-AP1 signaling pathways.

Influenza A viruses (IAV), significant respiratory pathogenic agents, cause seasonal epidemics and global pandemics in intra- and interannual cycles. Despite effective therapies targeting viral proteins, the continuous generation of drug-resistant IAV strains is challenging. Therefore, exploring novel host-specific antiviral treatment strategies is urgently needed. Here, we found that lidocaine, widely used for local anesthesia and sedation, significantly inhibited H1N1(PR8) replication in macrophages. Interestingly, its antiviral effect did not depend on the inhibition of voltage-gated sodium channels (VGSC), the main target of lidocaine for anesthesia. Lidocaine significantly upregulated early IFN-I, interferon α4 (IFNα4) mRNA, and protein levels, but not those of early IFNß in mouse RAW 264.7 cell line and human THP-1 derived macrophages. Knocking out IFNα4 by CRISPR-Cas9 partly reversed lidocaine's inhibition of PR8 replication in macrophages. Mechanistically, lidocaine upregulated IFNα4 by activating TANK-binding kinase 1 (TBK1)-IRF7 and JNK-AP1 signaling pathways. These findings indicate that lidocaine has an incredible antiviral potential by enhancing IFN-I signaling in macrophages. In conclusion, our results indicate the potential auxiliary role of lidocaine for anti-influenza A virus therapy and even for anti-SARS-CoV-2 virus therapy, especially in the absence of a specific medicine.

Traditional Chinese Medicine in Treatment of COVID-19 and Viral Disease: Efficacies and Clinical Evidence.

Coronavirus disease 2019 (COVID-19) remains an uncontained, worldwide pandemic. While battling the disease in China, the Chinese government has actively promoted the use of traditional Chinese medicine, and many studies have been conducted to determine the efficacy of traditional Chinese medicine for treating COVID-19. The present review discusses the effectiveness and safety of traditional Chinese medicine in curing COVID-19 and provides clinical evidence from all confirmed cases in China. Applications of traditional Chinese medicine and specific recipes for treating other viral infections, such as those caused by severe acute respiratory syndrome coronavirus and influenza A viruses (including H1N1), are also discussed. Studies have reported that traditional Chinese medicine treatment plays a significant role in improving clinical symptoms. Therefore, further investigation may be of high translational value in revealing novel targeted therapies for COVID-19.

SRSF5-Mediated Alternative Splicing of M Gene is Essential for Influenza A Virus Replication: A Host-Directed Target Against Influenza Virus.

Splicing of influenza A virus (IAV) RNA is an essential process in the viral life cycle that involves the co-opting of host factors. Here, it is demonstrated that induction of host serine and arginine-rich splicing factor 5 (SRSF5) by IAV facilitated viral replication by enhancing viral M mRNA splicing. Mechanistically, SRSF5 with its RRM2 domain directly bounds M mRNA at conserved sites (M mRNA position 163, 709, and 712), and interacts with U1 small nuclear ribonucleoprotein (snRNP) to promote M mRNA splicing and M2 production. Mutations introduced to the three binding sites, without changing amino acid code, significantly attenuates virus replication and pathogenesis in vivo. Likewise, SRSF5 conditional knockout in the lung protects mice against lethal IAV challenge. Furthermore, anidulafungin, an approved antifungal drug, is identified as an inhibitor of SRSF5 that effectively blocks IAV replication in vitro and in vivo. In conclusion, SRSF5 as an activator of M mRNA splicing promotes IAV replication and is a host-derived antiviral target.

A combination vaccine against SARS-CoV-2 and H1N1 influenza based on receptor binding domain trimerized by six-helix bundle fusion core.

BACKGROUND: Increasing severe morbidity and mortality by simultaneous or sequential infections with SARS-CoV-2 and influenza A viruses (IAV), especially in the elderly and obese patients, highlight the urgency of developing a combination vaccine against COVID-19 and influenza. METHODS: Self-assembling SARS-CoV-2 RBD-trimer and Influenza H1N1 HA1-trimer antigens were constructed, upon the stable fusion core in post-fusion conformation. Immunogenicity of SARS-CoV-2 RBD-trimer vaccine and H1N1 HA1-trimer antigens candidates were evaluated in mice. Protection efficacy of a combination vaccine candidate against SARS-CoV-2 and IAV challenge was identified using the K18-hACE2 mouse model. FINDINGS: Both the resultant RBD-trimer for SARS-CoV-2 and HA1-trimer for H1N1 influenza fully exposed receptor-binding motifs (RBM) or receptor-binding site (RBS). Two-dose RBD-trimer induced significantly higher binding and neutralizing antibody titers, and also a strong Th1/Th2 balanced cellular immune response in mice. Similarly, the HA1-trimer vaccine was confirmed to exhibit potent immunogenicity in mice. A combination vaccine candidate, composed of RBD-trimer and HA1-trimer, afforded high protection efficacy in mouse models against stringent lethal SARS-CoV-2 and homogenous H1N1 influenza co-infection, characterized by 100% survival rate. INTERPRETATION: Our results represent a proof of concept for a combined vaccine candidate based on trimerized receptor binding domain against co-epidemics of COVID-19 and influenza. FUNDING: This project was funded by the Strategic Priority Research Program of CAS (XDB29040201), the National Natural Science Foundation of China (81830050, 81901680, and 32070569) and China Postdoctoral Science Foundation (2021M703450).

Epidemics and pandemics of infectious disease

Throughout the course of civilization, epidemics and pandemics have ravaged humanity, destroyed animal breeding and horticulture, and has also changed the course of history. It has been estimated that Justinian plague has affected half of the population of Europe and killed in three pandemics 50 million people, the avian-borne flu (Spanish flu), resulted in 50 million deaths worldwide in the years 1918-1919, and recently the COVID-19 is officially a pandemic, after barreling through 114 countries in just three months. In the past, rinderpest has hit Europe with three long panzootics, African swine fever (ASF), is still a threat to both the swine production industry and the health of wild boar populations. Several molecular changes occur in the pathogen that may trigger an epidemic or even pandemic. These include increase of virulence, introduction into a novel host, and changes in host susceptibility to the pathogen. Once the infectious disease threat reaches an epidemic or pandemic level, the goal of the response is to mitigate its impact and reduce its incidence, morbidity and mortality as well as disruptions to economic, political, and social systems. An epidemic curve shows progression of illnesses in an outbreak over time and the SIR, SI, SIRD and SEIR represent the simplest compartmental models that enable simplify the mathematical modelling of epidemics. This article throws a light on changing ideas in epidemiology of infectious diseases.

Elucidating the enhanced binding affinity of a double mutant SP-D with trimannose on the influenza A virus using molecular dynamics.

Surfactant protein D (SP-D) is an essential component of the human pulmonary surfactant system, which is crucial in the innate immune response against glycan-containing pathogens, including Influenza A viruses (IAV) and SARS-CoV-2. Previous studies have shown that wild-type (WT) SP-D can bind IAV but exhibits poor antiviral activities. However, a double mutant (DM) SP-D consisting of two point mutations (Asp325Ala and Arg343Val) inhibits IAV more potently. Presently, the structural mechanisms behind the point mutations' effects on SP-D's binding affinity with viral surface glycans are not fully understood. Here we use microsecond-scale, full-atomistic molecular dynamics (MD) simulations to understand the molecular mechanism of mutation-induced SP-D's higher antiviral activity. We find that the Asp325Ala mutation promotes a trimannose conformational change to a more stable state. Arg343Val increases the binding with trimannose by increasing the hydrogen bonding interaction with Glu333. Free energy perturbation (FEP) binding free energy calculations indicate that the Arg343Val mutation contributes more to the increase of SP-D's binding affinity with trimannose than Asp325Ala. This study provides a molecular-level exploration of how the two mutations increase SP-D binding affinity with trimannose, which is vital for further developing preventative strategies for related diseases.

Synthesis of novel pyridine and pyrimidine thioglycoside phosphoramidates for the treatment of COVID-19 and influenza A viruses.

A novel series of pyridine, cytosine, and uracil thioglycoside analogs (4a-i, 9a,b, and 13a,b, respectively) and their corresponding phosphoramidates (6a-I, 10a,b, and 14a,b, respectively) were synthesized and assessed for their antiviral inhibitory activities in a dual-pathogen screening protocol against SARS-CoV-2 and influenza A virus (IAV). MTT cytotoxicity (TC50) and plaque reduction assays were used to explore inhibition and cytotoxicity percentage values for H5N1 influenza virus strain and the half-maximal cytotoxic concentration (CC50) and inhibitory concentration (IC50) for SARS-CoV-2 virus. Most of the tested compounds demonstrated dose-dependent inhibition behavior. Both cytosine thioglycoside phosphoramidates 10a and 10b exhibited the most potent profiles with 83% and 86% inhibition at 0.25 µM concentration against H5N1 and IC50 values of 12.16 µM, 14.9 µM against SARS-CoV-2, respectively. Moreover, compounds 10a and 10b have been shown to have the highest selectivity index (SI) among all the tested compounds against SARS-CoV-2 with 28.2 and 26.9 values, respectively.

Special Issue: Microbiologists making waves around the South Pacific. (Special Issue: Microbiologists making waves around the South Pacific.)

This special issue includes 11 articles focusing on development of container laboratories in response to COVID-19;COVID-19 in Fiji;Pacific Regional Infectious Disease Association (PRIDA) - capacity-building for microbiology and infectious disease across the Pacific;meningococcal surveillance in Southeast Asia and the Pacific;tropical fever in remote tropics;movement of arboviruses between Indonesia and Western Australia;Rotavirus surveillance informs diarrhoea disease burden in the WHO Western-Pacific region;surveillance for One Health and high consequence veterinary pathogens (Brucellosis, Coxiellosis and Foot and Mouth Disease) in Southeast Asia - Lao PDR and Cambodia in focus and the importance of international partnerships;Avian influenza H5N1.

Aerosol Transmission of the Pandemic SARS-CoV-2 and Influenza A Virus Was Blocked by Negative Ions.

The pandemic of respiratory diseases, such as coronavirus disease 2019 (COVID-19) and influenza, has imposed significant public health and economic burdens on the world. Wearing masks is an effective way to cut off the spread of the respiratory virus. However, due to cultural differences and uncomfortable wearing experiences, not everyone is willing to wear masks; there is an urgent need to find alternatives to masks. In this study, we tested the disinfection effect of a portable ionizer on pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (strain V34) and influenza A virus (strain CA04). Negative ions significantly reduced the concentration of particulate matter in the air above and effectively disinfected viruses stuck to the solid plate at the level of both nucleic acid and virus titer. The disinfection efficiency was >99.8% after 1-h exposure. Moreover, negative ions effectively disinfected aerosolized viruses; the disinfection efficiency was more than 87.77% after purification for 10 min. Furthermore, negative ions had a significant protective effect on susceptible animals exposed to viral aerosols. When the negative ionizer was switched from off to on, the inhalation 50% infective dose (ID50) for golden hamsters challenged with SARS-CoV-2 rose from 9.878 median tissue culture infective dose (TCID50) [95% confidence interval (CI), 6.727-14.013 TCID50] to 43.891 TCID50 (95% CI, 29.31-76.983 TCID50), and the inhalation ID50 for guinea pigs challenged with influenza A virus rose from 6.696 TCID50 (95% CI, 3.251-9.601 TCID50) to 28.284 TCID50 (95% CI, 19.705-40.599 TCID50). In the experiment of transmission between susceptible animals, negative ions 100% inhibited the aerosol transmission of SARS-CoV-2 and influenza A virus. Finally, we tested the safety of negative ion exposure. Balb/c mice exposed to negative ions for 4 weeks showed no abnormalities in body weight, blood routine analysis, and lung pathology. Our study demonstrates that air ions can be used as a safe and effective means of blocking respiratory virus transmission and contribute to pandemic prevention and control.

Lessons learned from coronavirus pandemic

Since the day I started to write this article, there have been so many new developments in the world and in our country, even in the last 4 days, evaluating new information, reading what is written, making sense of interpretations, causes ones thoughts to jump from one point to another. I realized that it is not possible to prepare a systematic article that covers the subject completely. I started by making a list of messages and observations in my mind and sharing them with you. The pandemic experience was not the first in our working life, but the closest was the H1N1 pandemic in the 2009-2010 season. In our country, a total of 13,591 cases and 656 deaths due to pandemic influenza virus were confirmed. Hospitalization rate was 1.4%;the rate of hospitalization to intensive care unit was 13.6% and the mortality rate in intensive care patients was 19.6%.

Summary of national data of class A, B and C communicable diseases in China, October 2021

In October 2021 (from 00: 00, 1 October to 24: 00, 31 October), a total of 523 006 cases of notifiable communicable diseases, including 2 040 deaths, were reported in China (except Hong Kong, Macao Special Administrative Regions and Taiwan Province, the same below). In communicable diseases in class A, 2 cases of cholera were reported without death. In communicable diseases in class B, no cases and no deaths of severe acute respiratory syndrome, poliomyelitis, human infection with highly pathogenic avian influenza virus, diphtheria and human infection with avian influenza A (H7N9) virus were reported. For the remaining 22 communicable diseases in class B, 249 605 cases were reported, a decrease of 8% compared with last month (272 332 cases) and a decrease of 3% compared with the same period in 2020 (258 591 cases). The first 5 diseases in terms of reported case number were viral hepatitis, pulmonary tuberculosis, syphilis, gonorrhea and AIDS, accounting for 95% of the total reported cases in class B. A total of 2 039 deaths were reported, a decrease of 6% (133 deaths) compared with last month (2 172 deaths) and an increase of 17% compared with the same period in 2020 (1 737 deaths). According to the website of the National Health Commission of China, a total of 1 081 confirmed COVID-19 cases were reported, without death, by 31 provinces (municipalities, autonomous regions) and Xinjiang Production and Construction Corps from 00: 00, 1 October to 24: 00, 31 October, 2021. In class C communicable diseases, a total of 273 399 cases were reported, an increase of 20% compared with last month (228 597 cases) and a decrease of 13% compared with the same period in 2020 (315 366 cases). The first 3 diseases in terms of reported case number were hand foot and mouth disease (HFMD), other infectious diarrhea and influenza, accounting for 95% of the total reported cases in class C. Compared with last month, except filariasis which had no incidences in both months, the diseases with reported cases increases were HFMD (45 435 cases, 52%), influenza (17 811 cases, 50%) and rubella (11 cases, 12%), but the reported cases of other diseases all decreased, the diseases with obvious case decreases were other infectious diarrhea (16 519 cases, 18%), mumps (1 490 cases, 12%) and acute hemorrhagic conjunctivitis (327 cases, 14%). Compared with the same period in 2020, except filariasis which had no incidences in both years, the diseases with reported case increases were influenza (33 177 cases, 164%), typhus fever (15 cases, 9%), rubella (8 cases, 9%) and leprosy (3 cases, 17%), but the diseases with reported case decreases were HFMD (65 002 cases, 33%), other infectious diarrhea (4 111 cases, 5%) and mumps (1 574 cases, 12%). One death caused by class C communicable diseases was reported, an increase of 1 death compared with last month and a decrease of 1 death compared with the same period in 2020 (2 deaths).

Summary of national data of class A, B and C communicable diseases in China, September 2021

In September 2021 (from 00:00, 1 September to 24: 00, 30 September), a total of 500 929 cases of notifiable communicable diseases, including 2 172 deaths, were reported in China (except Hong Kong, Macao Special Administrative Regions and Taiwan Province, the same below). In communicable diseases in class A, no case and no death were reported. In communicable diseases in class B, no cases and no deaths of severe acute respiratory syndrome, poliomyelitis, human infection with highly pathogenic avian influenza virus, diphtheria and human infection with avian influenza A(H7N9) virus were reported. For the remaining 22 communicable diseases in class B, 272 332 cases were reported, a decrease of 0.9% compared with last month (274 917 cases) and a decrease of 5% compared with the same period in 2020 (287 923 cases). The first 5 diseases in terms of reported case number were viral hepatitis, pulmonary tuberculosis, syphilis, gonorrhea and brucellosis, accounting for 94% of the total reported cases in class B. A total of 2 172 deaths were reported, an increase of 5% (95 deaths) compared with last month (2 077 deaths) and a decrease of 5% compared with the same period in 2020 (2 291 deaths). According to the website of the National Health Commission of China, a total of 1 264 confirmed COVID-19 cases were reported, without death, by 31 provinces (municipalities, autonomous regions) and Xinjiang Production and Construction Corps from 00:00, 1 September to 24: 00, 30 September, 2021. In class C communicable diseases, a total of 228 597 cases were reported, an increase of 10% compared with last month (207 153 cases) and a decrease of 7% compared with the same period in 2020 (247 112 cases). The first 3 diseases in terms of reported case number were other infectious diarrhea, hand foot and mouth disease (HFMD) and influenza, accounting for 93% of the total reported cases in class C. Compared with last month, except filariasis, visceral leishmaniasis, leprosy and other infectious diarrhea which decreased by 1 case, 11 cases (39%), 12 cases (33%) and 12 747 cases (12%) respectively, the reported cases of all other diseases increased, the diseases with obvious case increases were HFMD (15 352 cases, 22%), influenza (14 160 cases, 66%) and mumps (4 253 cases, 51%). Compared with the same period in 2020, the diseases with reported case increases were influenza (17 269 cases, 95%), visceral leishmaniasis (4 cases, 31%), rubella (19 cases, 27%) and typhus fever (32 cases, 18%), filariasis had no incidences in both years, and the diseases with obvious reported case decreases were HFMD (26 506 cases, 23%). other infectious diarrhea (5 628 cases, 6%) and mumps (523 cases, 4%). No death caused by class C communicable diseases was reported, same to the last month and a decrease of 3 deaths compared with the same period in 2020 (3 deaths).

Electrochemical investigations for COVID-19 detection-A comparison with other viral detection methods.

Virus-induced infection such as SARS-CoV-2 is a serious threat to human health and the economic setback of the world. Continued advances in the development of technologies are required before the viruses undergo mutation. The low concentration of viruses in environmental samples makes the detection extremely challenging; simple, accurate and rapid detection methods are in urgent need. Of all the analytical techniques, electrochemical methods have the established capabilities to address the issues. Particularly, the integration of nanotechnology would allow miniature devices to be made available at the point-of-care. This review outlines the capabilities of electrochemical methods in conjunction with nanotechnology for the detection of SARS-CoV-2. Future directions and challenges of the electrochemical biosensors for pathogen detection are covered including wearable and conformal biosensors, detection of plant pathogens, multiplexed detection, and reusable biosensors for on-site monitoring, thereby providing low-cost and disposable biosensors.

Comparative review of respiratory diseases caused by coronaviruses and influenza A viruses during epidemic season.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to sweep the world, causing infection of millions and death of hundreds of thousands. The respiratory disease that it caused, COVID-19 (stands for coronavirus disease in 2019), has similar clinical symptoms with other two CoV diseases, severe acute respiratory syndrome and Middle East respiratory syndrome (SARS and MERS), of which causative viruses are SARS-CoV and MERS-CoV, respectively. These three CoVs resulting diseases also share many clinical symptoms with other respiratory diseases caused by influenza A viruses (IAVs). Since both CoVs and IAVs are general pathogens responsible for seasonal cold, in the next few months, during the changing of seasons, clinicians and public heath may have to distinguish COVID-19 pneumonia from other kinds of viral pneumonia. This is a discussion and comparison of the virus structures, transmission characteristics, clinical symptoms, diagnosis, pathological changes, treatment and prevention of the two kinds of viruses, CoVs and IAVs. It hopes to provide information for practitioners in the medical field during the epidemic season.