Emergence and re-emergence of respiratory virus infections represent a significant threat to global public health, as they occur seasonally and less frequently (such as in the case of influenza virus) as pandemic infections. Some of these viruses have been in the human population for centuries and others had recently emerged as a public health problem. Influenza viruses have been affecting the human population for a long time now; however, their ability to rapidly evolve through antigenic drift and antigenic shift causes the emergence of new strains. A recent example of these events is the avian-origin H7N9 influenza virus outbreak currently undergoing in China. Human H7N9 influenza viruses are resistant to amantadines and some strains are also resistant to neuraminidase inhibitors greatly limiting the options for treatment. Respiratory syncytial virus (RSV) may cause a lower respiratory tract infection characterized by bronchiolitis and pneumonia mainly in children and the elderly. Infection with RSV can cause severe disease and even death, imposing a severe burden for pediatric and geriatric health systems worldwide. Treatment for RSV is mainly supportive since the only approved therapy, a monoclonal antibody, is recommended for prophylactic use in high-risk patients. The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging respiratory virus. The virus was first recognized in 2012 and it is associated with a lower respiratory tract disease that is more severe in patients with comorbidities. No licensed vaccines or antivirals have been yet approved for the treatment of MERS-CoV in humans. It is clear that the discovery and development of novel antivirals that can be used alone or in combination with existing therapies to treat these important respiratory viral infections are critical. In this review, we will describe some of the novel therapeutics currently under development for the treatment of these infections.

Hemagglutination inhibition (HI) titers are a major correlate of protection for influenza-related illness. The influenza virus hemagglutinin possesses antigenic sites that are the targets of HI active antibodies. Here, a panel of mutant viruses each lacking a classically defined antigenic site was created to compare the species-specific immunodominance of the antigenic sites in a clinically relevant hemagglutinin. HI active antibodies of antisera from influenza virus–infected mice targeted sites Sb and Ca2. HI active antibodies of guinea pigs were not directed against any specific antigenic site, although trends were observed toward Sb, Ca2, and Sa. HI titers of antisera from infected ferrets were significantly affected by site Sa. HI active antibodies of adult humans followed yet another immunodominance pattern, in which sites Sb and Sa were immunodominant. When comparing the HI profiles among different species by antigenic cartography, animals and humans grouped separately. This study provides characterizations of the antibody-mediated immune responses against the head domain of a recent H1 hemagglutinin in animals and humans.

Vaccines and first-generation antiviral therapeutics have provided important protection against COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there remains a need for additional therapeutic options that provide enhanced efficacy and protection against potential viral resistance. The SARS-CoV-2 papain-like protease (PL ^pro ) is one of the two essential cysteine proteases involved in viral replication. While inhibitors of the SARS-CoV-2 main protease have demonstrated clinical efficacy, known PL ^pro inhibitors have, to date, lacked the inhibitory potency and requisite pharmacokinetics to demonstrate that targeting PL ^pro translates to in vivo efficacy in a preclinical setting. Here, we report the machine learning–driven discovery of potent, selective, and orally available SARS-CoV-2 PL ^pro inhibitors, with lead compound PF-07957472 ( 4 ) providing robust efficacy in a mouse-adapted model of COVID-19 infection.

Licensed influenza virus vaccines target the head domain of the hemagglutinin (HA) glycoprotein which undergoes constant antigenic drift. The highly conserved HA stalk domain is an attractive target to increase immunologic breadth required for universal influenza virus vaccines. We tested the hypothesis that immunization with a pandemic influenza virus vaccine boosts pre-existing anti-stalk antibodies. We used chimeric cH6/1, full length H2 and H18 HA antigens in an ELISA to measure anti-stalk antibodies in recipients participating in clinical trials of A/H1N1, A/H5N1 and A/H9N2 vaccines. The vaccines induced high titers of anti-H1 stalk antibodies in adults and children, with higher titers elicited by AS03-adjuvanted vaccines. We also observed cross-reactivity to H2 and H18 HAs. The A/H9N2 vaccine elicited plasmablast and memory B-cell responses. Post-vaccination serum from vaccinees protected mice against lethal challenge with cH6/1N5 and cH5/3N4 viruses. These findings support the concept of a chimeric HA stalk-based universal influenza virus vaccine. clinicaltrials.gov: NCT02415842.

West Nile virus (WNV) and Zika virus (ZIKV) are mosquito-borne viral infections. Over the past few decades, WNV has been associated with several outbreaks involving high numbers of neuroinvasive diseases among humans. The recent re-emergence of ZIKV has been associated with congenital malformation and also with Guillain–Barre syndrome in adults. The geographic range of arthropod-borne viruses has been rapidly increasing in recent years. The objectives of this study were to determine the presence of IgG specific antibodies and the genome of WNV and ZIKV in human samples, as well as WNV and ZIKV genomes in wild-caught mosquitoes in urban and rural areas of the Hormozgan province, in southern Iran. A total of 494 serum samples were tested for the presence of WNV and ZIKV IgG antibodies using ELISA assays. One hundred and two (20.6%) samples were reactive for WNV IgG antibodies. All serum samples were negative for ZIKV IgG antibodies. Using the multivariable logistic analysis, age (45+ vs. 1–25; OR = 3.4, 95% C.I.: 1.8–6.3), occupation (mostly outdoor vs. mostly indoor; OR = 2.4, 95% C.I.: 1.1–5.2), and skin type(type I/II vs. type III/IV and type V/VI; OR = 4.3, 95% C.I.: 1.7–10.8 and OR = 2.7, 95% C.I.: 1.3–5.5 respectively, skin types based on Fitzpatrick scale) showed significant association with WNV seroreactivity. We collected 2,015 mosquitoes in 136 pools belonging to 5 genera and 14 species. Three pools of Culex pipiens complex were positive for WNV RNA using real-time reverse transcription polymerase chain reaction (rtRT-PCR). ZIKV RNA was not detected in any of the pools. All WNV ELISA reactive serum samples were negative for WNV RNA. In conclusion, we provided evidence of the establishment of WNV in southern Iran and no proof of ZIKV in serum samples or in mosquito vectors. The establishment of an organized arbovirus surveillance system and active case finding strategies seems to be necessary. In recent decades mosquito-borne viruses have reached and adapted to new habitats, and now they can be found in nearly all continents. Facilitated goods transportation, live stock exchange, people travelling more easily, and most importantly world climate alterations, might be some of the reasons for this mosquito habitat spreading. Emergence of WNV in North America, Europe, and most Mediterranean countries like Turkey, Greece and Israel is evidence of this spreading. Furthermore, emergence and re-emergence of some of these mosquito borne viruses in new areas may be accompanied with changes in their pre-known pathogenesis. Re-emergence of ZIKV in the South Pacific and America from 2007 to 2016 was accompanied with an increase in neurovirulent diseases and congenital malformations. In this study, we evaluated the presence of WNV and ZIKV via serological and genome detection in human samples and mosquitoes (viral genome analysis) from southern Iran. This region is on the coast with a warm and tropical climate suitable for inhabitation and expansion of the vectors harboring these two viruses. We caught a large spectrum of mosquitoes from these areas. After classification, we analyzed the mosquitoes’ pools for WNV and ZIKV genomic RNA. Our results showed that 20.6% of the studied human samples were IgG reactive to WNV while no antibodies against ZIKV were detected. We found WNV RNA genome in three mosquitoes’ pools. The genomic analysis was negative for ZIKV in both human and mosquito samples. Based on the results WNV is notably circulating in southern Iran; while no evidence of ZIKV infection in people or circulation in any of the vectors was observed.