Broad Spectrum Of Viruses Research Articles

In Vitro Antiviral Activity of Kalanchoe daigremontiana Extract against Human Herpesvirus Type 1.

Plant polyphenols possess diverse bioactivities, including antiviral activity against a broad spectrum of viruses. Here, we investigated the virucidal properties of an Kalanchoe daigremontiana extract using an in vitro model of human herpesvirus type 1 (HHV-1) infection. Chromatographic analysis indicated that the extract of Kalanchoe daigremontiana is rich in various compounds, among which are polyphenols with virucidal activity confirmed in the literature. We found that Kalanchoe daigremontiana extract shows an ability to prevent HHV-1 infection by direct inhibition of the virus attachment, penetration, and blocking of infection when used in pretreatment or post-entry treatment. Our results indicate that Kalanchoe daigremontiana extract may be a good candidate drug against HHV-1, both as a substance to prevent infection and to treat an already ongoing infection. Our findings illustrate that Kalanchoe daigremontiana could be a potential new candidate for clinical consideration in the treatment of HHV-1 infection alone or in combination with other therapeutics.

Analytical Profile of Antiviral Drugs-Remdesivir, Simeprevir, and Sofosbuvir: A Review

Remdesivir (RDV) is an antiviral drug and a phosphonamidite prodrug designed to have activity against a broad spectrum of viruses, act as a nucleoside analogue, and inhibit the RNA-dependent RNA polymerase [RDRP] of coronaviruses, including SARS-CoV-2, whereas Simeprevir (SMV) and Sofosbuvir (SFS) are direct-acting antiviral drugs approved for the treatment of chronic Hepatitis C virus (HCV) infection. Reports show that the structure and replication mechanism of HCV and SARS-COV-2 are comparable. Hepatitis C virus protease inhibitors include Simeprevir. Because it is an NS3/4A protease inhibitor, it inhibits protein synthesis, which stops viruses from maturing. A nucleotide analogue inhibitor called sofosbuvir selectively blocks the RNA-dependent RNA polymerase of HCV NS5B (non-structural protein 5B). This review article gathers and discusses the range of analytical techniques—UV, HPLC, and hyphenated procedures like LC-MS—that are available in the literature for the determination of RDV, SMV, and SFS. This review article can be effectively explored to conduct future analytical investigation for the estimation of the selected drugs in pharmaceutical and biological samples.

Mucus-Inspired Self-Healing Hydrogels: A Protective Barrier for Cells against Viral Infection.

Mucus is a dynamic biological hydrogel, composed primarily of the glycoprotein mucin, exhibits unique biophysical properties and forms a barrier protecting cells against a broad-spectrum of viruses. Here, this work develops a polyglycerol sulfate-based dendronized mucin-inspired copolymer (MICP-1) with ≈10% repeating units of activated disulfide as cross-linking sites. Cryo-electron microscopy (Cryo-EM)analysis of MICP-1 reveals an elongated single-chain fiber morphology. MICP-1 shows potential inhibitory activity against many viruses such as herpes simplex virus 1 (HSV-1) and SARS-CoV-2 (including variants such as Delta and Omicron). MICP-1 produces hydrogels with viscoelastic properties similar to healthy human sputum and with tuneable microstructures using linear and branched polyethylene glycol-thiol (PEG-thiol) as cross-linkers. Single particle tracking microrheology, electron paramagnetic resonance (EPR) and cryo-scanning electron microscopy (Cryo-SEM) are used to characterize the network structures. The synthesized hydrogels exhibit self-healing properties, along with viscoelastic properties that are tuneable through reduction. A transwell assay is used to investigate the hydrogel's protective properties against viral infection against HSV-1. Live-cell microscopy confirms that these hydrogels can protect underlying cells from infection by trapping the virus, due to both network morphology and anionic multivalent effects. Overall, this novel mucin-inspired copolymer generates mucus-mimetic hydrogels on a multi-gram scale. These hydrogels can be used as models for disulfide-rich airway mucus research, and as biomaterials.

Broad-spectrum dengue virus detection using the commercial RealStar dengue RT-PCR kit 3.0 (Altona) and an in-house combined real-time RT-PCR assay

In endemic areas, the genetic diversity among co-circulating dengue virus (DENV) strains is considerable and new, highly divergent strains are identified on a regular basis. It is thus critical to ensure that molecular diagnostic tools effectively detect virus genomes even in case of important genetic variation. Here, we tested both the pan-DENV detection capacity and the limit of detection of two real-time RT-PCR assays: (i) the commercial RealStar Altona 3.0 system and (ii) a laboratory developed test (LDT) combining two RT-PCR systems in a single reaction tube (DenAllDUO). We used a panel of DENV strains representative of the genetic diversity within DENV species, combined with three in vitro transcribed RNAs as surrogates for unavailable strains corresponding to recently discovered strains with substantial genetic divergence: DENV serotype 1 (DENV-1) Brun2014, DENV-2 QML22 and DENV-4 DKE121. Both systems (i) targeted the genome 3′ untranslated region, (ii) displayed a broad detection spectrum, encompassing most of DENV species diversity, and (iii) detected the three aforementioned divergent strains. DenAllDUO detected all the strains tested, whereas the RealStar system failed to detect strains from DENV-4 genotype III. Altogether, our findings support the value of these two RT-PCR systems as part of the Dengue diagnostic arsenal.

Oreoch-1: A broad-spectrum virus and host-targeting peptide against animal infections.

In recent decades, the global rise of viral emerging infectious diseases has posed a substantial threat to both human and animal health worldwide. The rapid spread and accumulation of mutations into viruses, and the limited availability of antiviral drugs and vaccines, stress the urgent need for alternative therapeutic strategies. Antimicrobial peptides (AMPs) derived from natural sources present a promising avenue due to their specificity and effectiveness against a broad spectrum of pathogens. The present study focuses on investigating the antiviral potential of oreochromicin-1 (oreoch-1), a fish-derived AMP obtained from Nile tilapia, against a wide panel of animal viruses including canine distemper virus (CDV), Schmallenberg virus (SBV), caprine herpesvirus 1 (CpHV-1), and bovine herpesvirus 1 (BoHV-1). Oreoch-1 exhibited a strong antiviral effect, demonstrating an inhibition of infection at concentrations in the micromolar range. The mechanism of action involves the interference with viral entry into host cells and a direct interaction between oreoch-1 and the viral envelope. In addition, we observed that the peptide could also interact with the cell during the CDV infection. These findings not only highlight the efficacy of oreoch-1 in inhibiting viral infection but also emphasize the potential of fish-derived peptides, specifically oreoch-1, as effective antiviral agents against viral infections affecting animals, whose potential to spill into humans is high. This research contributes valuable insights to the ongoing quest for novel antiviral drugs with the potential to mitigate the impact of infectious diseases on a global scale.

Disparate viral pandemics from COVID19 to monkeypox and beyond: a simple, effective and universal therapeutic approach hiding in plain sight.

The field of antiviral therapeutics is fixated on COVID19 and rightly so as the fatalities at the height of the pandemic in the United States were almost 1,000,000 in a twelve month period spanning parts of 2020/2021.A coronavirus called SARS-CoV2 is the causative virus. Development of a vaccine through molecular biology approaches with mRNA as the inducer of virus spike protein has played a major role in driving down mortality and morbidity. Antivirals have been of marginal value in established infections at the level of hospitalization. Thus, the current focus is on early symptomatic infection of about the first five days. The Pfizer drug paxlovid which is composed of nirmatrelvir, a peptidomimetic protease inhibitor of SARS-CoV2 Mpro enzyme, and ritonavir to retard degradation of nirmatrelvir, is the current FDA recommended treatment of early COVID19. There is no evidence of broad antiviral activity of paxlovid against other diverse viruses such as the influenza virus, poxviruses, as well as a host of respiratory viruses. Although type I interferons (IFNs) are effective against SARS-CoV2 in cell cultures and in early COVID19 infections, they have not been broadly recommended as therapeutics for COVID19. We have developed stable peptidomimetics of both types I and II IFNs based on our noncanonical model of IFN signaling involving the C-terminus of the IFNs. We have also identified two members of intracellular checkpoint inhibitors called suppressors of cytokine signaling (SOCS), SOCS1 and SOCS3 (SOCS1/3), and shown that they are virus induced intrinsic virulence proteins with activity against IFN signaling enzymes JAK2 and TYK2. We developed a peptidomimetic antagonist, based on JAK2 activation loop, against SOCS1/3 and showed that it synergizes with the IFN mimetics for potent broad spectrum antiviral activity without the toxicity of intact IFN molecules. IFN mimetics and the SOCS1/3 antagonist should have an advantage over currently used antivirals in terms of safety and potency against a broad spectrum of viruses.

Synthesis, Antiviral and Cytostatic Activity of New Series of Naphthalimide Derivatives

A new series of N-(diethylphosphonoalkyl)-1,8-naphthalimides were synthesized via direct reaction of 1,8-naphthalic anhydride or its 3-nitro- and 4-bromo- derivatives with selected ɷ-aminoalkylphosphonates and evaluated against a broad-spectrum of viruses as well as for their cytostatic properties toward selected cell lines. N-(diethylphosphonomethyl)-3-nitro-1,8-naphthalimide 15a exhibited inhibitory activity toward coxsackie virus B4 in Vero cells (EC50 = 9.45 μM), whereas 3-nitro-1,8-naphthalimides 15b and 15d containing short 2-carbon linker showed moderate activity against herpes simplex virus-2 (G) and herpes simplex virus-1 TK– KOS ACVr. Furthermore, compounds 15a, 15b and 15d showed antiviral potency against human coronavirus. Several naphthalimides exhibited cytostatic activity toward tested cancerous cell lines as well as normal retina cells. Transformation of selected diethyl phosphonates 13, 14 and 15 into ammonium phosphonates 21, 22 and 23 improved the solubility, however, did not result in the enhancement of antiviral and cytostatic potency of the compounds.

Characterization of non-neutralizing human monoclonal antibodies that target the M1 and NP of influenza A viruses.

Currently, many groups are focusing on isolating both neutralizing and non-neutralizing antibodies to the mutation-prone hemagglutinin as a tool to treat or prevent influenza virus infection. Less is known about the level of protection induced by non-neutralizing antibodies that target conserved internal influenza virus proteins. Such non-neutralizing antibodies could provide an alternative pathway to induce broad cross-reactive protection against multiple influenza virus serotypes and subtypes by partially overcoming influenza virus escape mediated by antigenic drift and shift. Accordingly, more information about the level of protection and potential mechanism(s) of action of non-neutralizing antibodies targeting internal influenza virus proteins could be useful for the design of broadly protective and universal influenza virus vaccines.

Deuremidevir and Simnotrelvir-Ritonavir for the Treatment of COVID-19.

Deuremidevir hydrobromide tablets and simnotrelvir tablets/ritonavir tablets (co-packaged) were approved by the Chinese National Medical Products Administration for the treatment of mild to moderate COVID-19 in January 2023. Both formulations contain small-molecule anti-SARS-CoV-2 agents. Deuremidevir, an oral nucleoside analog, is a broad-spectrum virus replication inhibitor targeting the highly conserved RNA-dependent RNA polymerase. Simnotrelvir-ritonavir is a co-packaged combination drug consisting of simnotrelvir tablets and ritonavir tablets. Simnotrelvir is an oral antiviral agent targeting the 3-chymotrypsin-like protease, which is essential for SARS-CoV-2 viral replication. Previous clinical trials revealed that both deuremidevir and simnotrelvir-ritonavir were effective and well tolerated in the treatment of COVID-19.

Plant virus resistance biotechnological approaches: From genes to the CRISPR/Cas gene editing system

Plant viruses cause crop losses in agronomically and economically important crops, making global food security a challenge. Although traditional plant breeding has been effective in controlling plant viral diseases, it is unlikely to solve the problems associated with the frequent emergence of new and more virulent virus species or strains. As a result, there is an urgent need to develop alternative virus control strategies that can be used to more easily contain viral diseases. A better understanding of plant defence mechanisms will open up new avenues for research into plant- pathogen interactions and the development of broad-spectrum virus resistance. The scientific literature was evaluated and structured in this review, and the results of the reliability of the methods of analysis used were filtered. As a result, we described the molecular mechanisms by which viruses interact with host plant cells. To develop an effective strategy for the control of plant pathogens with a significant intensity on the agricultural market, clear and standardised recommendations are required. The current review will provide key insights into the molecular underpinnings underlying the coordination of plant disease resistance, such as main classes of resistance genes, RNA interference, and the RNA-mediated adaptive immune system of bacteria and archaea – clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated Cas proteins – CRISPR/Cas. Future issues related to resistance to plant viral diseases will largely depend on integrated research to transfer fundamental knowledge to applied problems, bridging the gap between laboratory and field work.

Panchkarma in Janpadodhwansa w.s.r. COVID-19 and Its Documentation from Ayurvedic Texts

COVID-19 has emerged as a public health crisis and has done caused a disaster at multiple -levels. Manual retrieval of ancient books of Ayurveda was carried out. In From an Ayurvedic point of view, its very difficult to correlate COVID-19 with Aayurvedic terminology, on the basis of causes, symptoms, and complications., Iit can be correlated with various diseases like Janpadodhwansha(~epidemic), Shwasa(respiratory disease), pranaavrit vata(subtype of vata that is seated in head), dushi-visha(~cumulative), jwara-sannipattika (~severe fever), vata-kaphaja jwar (fever) , shwasana (~pneumonia), Abhisangaj jwar ( ~fever caused by virus or evil spirit), majjadhatugata jwar (~vitiated regulatory factors are located in structural component of bone marrow ) &and kasa roga (coughing). Treatment in such conditions is mentioned as Panchkarma (~detoxification procedure) . The main goal in such type of condition is to remove avarana (overlapping) so that Vayu (air) returns to normal functioning. Five detoxification procedures were also reported to be effective against a broad spectrum of viruses, including human immunodeficiency virus, herpes viruses, etc. Ayurvedic detoxification procedures can add an additive effect in to the managing COVID-19 through multiple modules, like as prophylactic and, curative treatment. Implementation of suggested influence or mode of action probably come up with empirical discernment escalating the Ayurveda other than prophylactic medical management and system considering alike ailments.

Chemically Modified Bovine β-Lactoglobulin as a Broad-Spectrum Influenza Virus Entry Inhibitor with the Potential to Combat Influenza Outbreaks.

Frequent outbreaks of the highly pathogenic influenza A virus (AIV) infection, together with the lack of broad-spectrum influenza vaccines, call for the development of broad-spectrum prophylactic agents. Previously, 3-hydroxyphthalic anhydride-modified bovine β-lactoglobulin (3HP-β-LG) was proven to be effective against human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it has also been used in the clinical control of cervical human papillomavirus (HPV) infections. Here, we show its efficacy in potently inhibiting infection by divergent influenza A and B viruses. Mechanistic studies suggest that 3HP-β-LG binds, possibly through its negatively charged residues, to the receptor-binding domain in the hemagglutinin 1 (HA1) subunit in the HA of the influenza virus, thus inhibiting the attachment of the HA to sialic acid on host cells. The intranasal administration of 3HP-β-LG led to the protection of mice against challenges by influenza A(H1N1)/PR8, A(H3N2), and A(H7N9) viruses. Furthermore, 3HP-β-LG is highly stable when stored at 50 °C for 30 days and it shows excellent safety in vitro and in vivo. Collectively, our findings suggest that 3HP-β-LG could be successfully repurposed as an intranasal prophylactic agent to prevent influenza virus infections during influenza outbreaks.

New insights into the antiviral activity of nordihydroguaiaretic acid: Inhibition of dengue virus serotype 1 replication

BackgroundDengue virus (DENV) is considered one of the most important pathogens in the world causing 390 million infections each year. Currently, the development of vaccines against DENV presents some shortcomings and there is no antiviral therapy available for its infection. An important challenge is that both treatments and vaccines must be effective against all four DENV serotypes. Nordihydroguaiaretic acid (NDGA), isolated from Larrea divaricata Cav. (Zygophyllaceae) has shown a significant inhibitory effect on a broad spectrum of viruses, including DENV serotypes 2 and 4. PurposeWe evaluated the in vitro virucidal and antiviral activity of NDGA on DENV serotype 1 (DENV1), including the study of its mechanism of action, to provide more evidence on its antiviral activity. MethodsThe viability of viral particles was quantified by the plaque-forming unit reduction method. NDGA effects on DENV1 genome and viral proteins were evaluated by qPCR and immunofluorescence, respectively. Lysosomotropic activity was assayed using acridine orange and neutral red dyes. ResultsNDGA showed in vitro virucidal and antiviral activity against DENV1. The antiviral effect would be effective within the first 2 h after viral internalization, when the uncoating process takes place. In addition, we determined by qPCR that NDGA decreases the amount of intracellular RNA of DENV1 and, by immunofluorescence, the number of cells infected. These results indicate that the antiviral effect of NDGA would have an intracellular mechanism of action, which is consistent with its ability to be incorporated into host cells. Considering the inhibitory activity of NDGA on the cellular lipid metabolism, we compared the antiviral effect of two inhibitors acting on two different pathways of this type of metabolism: 1) resveratrol that inhibits the sterol regulatory element of binding proteins, and 2) caffeic acid that inhibits the 5-lipoxygenase (5-LOX) enzyme. Only caffeic acid produced an inhibitory effect on DENV1 infection. We studied the lysosomotropic activity of NDGA on host cells and found, for the first time, that this compound inhibited the acidification of cell vesicles which would prevent DENV1 uncoating process. ConclusionThe present work contributes to the knowledge of NDGA activity on DENV. We describe its activity on DENV1, a serotype different to those that have been already reported. Moreover, we provide evidence on which stage/s of the viral replication cycle NDGA exerts its effects. We suggest that the mechanism of action of NDGA on DENV1 is related to its lysosomotropic effect, which inhibits the viral uncoating process.

The key micronutrient copper orchestrates broad-spectrum virus resistance in rice.

Copper is a critical regulator of plant growth and development. However, the mechanisms by which copper responds to virus invasion are unclear. We previously showed that SPL9-mediated transcriptional activation of miR528 adds a previously unidentified regulatory layer to the established ARGONAUTE (AGO18)-miR528-L-ascorbate oxidase (AO) antiviral defense. Here, we report that rice promotes copper accumulation in shoots by inducing copper transporter genes, including HMA5 and COPT, to counteract viral infection. Copper suppresses the transcriptional activation of miR528 by inhibiting the protein level of SPL9, thus alleviating miR528-mediated cleavage of AO transcripts to strengthen the antiviral response. Loss-of-function mutations in HMA5, COPT1, and COPT5 caused a significant reduction in copper accumulation and plant viral resistance because of the increased SPL9-mediated miR528 transcription. Gain in viral susceptibility was mitigated when SPL9 was mutated in the hma5 mutant background. Our study elucidates the molecular mechanisms and regulatory networks of copper homeostasis and the SPL9-miR528-AO antiviral pathway.

Advances in Research on Antiviral Activities of Sulfated Polysaccharides from Seaweeds.

In recent years, various viral diseases have suddenly erupted, resulting in widespread infection and death. A variety of biological activities from marine natural products have gradually attracted the attention of people. Seaweeds have a wide range of sources, huge output, and high economic benefits. This is very promising in the pharmaceutical industry. In particular, sulfated polysaccharides derived from seaweeds, considered a potential source of bioactive compounds for drug development, have shown antiviral activity against a broad spectrum of viruses, mainly including common DNA viruses and RNA viruses. In addition, sulfated polysaccharides can also improve the body’s immunity. This review focuses on recent advances in antiviral research on the sulfated polysaccharides from seaweeds, including carrageenan, galactan, fucoidan, alginate, ulvan, p-KG03, naviculan, and calcium spirulan. We hope that this review will provide new ideas for the development of COVID-19 therapeutics and vaccines.

Investigation of Avian Influenza H5N6 Virus-like Particles as a Broad-Spectrum Vaccine Candidate against H5Nx Viruses.

Highly pathogenic avian influenza (HPAI) clade 2.3.4.4 viruses have been reported to be the source of infections in several outbreaks in the past decades. In a previous study, we screened out a broad-spectrum virus strain, H5N6-Sichuan subtype, by using a lentiviral pseudovirus system. In this project, we aimed to investigate the potential of H5N6 virus-like particles (VLPs) serving as a broad-spectrum vaccine candidate against H5Nx viruses. We cloned the full-length M1 gene and H5, N6 genes derived from the H5N6-Sichuan into pFASTBac vector and generated the VLPs using the baculovirus-insect cell system. H5N6 VLPs were purified by sucrose gradient centrifugation, and the presence of H5, N6 and M1 proteins was verified by Western blot and SDS-PAGE. The hemagglutination titer of H5N6 VLPs after purification reached 5120 and the particle structure remained as viewed by electron microscopy. The H5N6 VLPs and 293T mammalian cell-expressed H5+N6 proteins were sent for mice immunization. Antisera against the H5+N6 protein showed 80 to 320 neutralizing antibody titers to various H5Nx pseudoviruses. In contrast, H5N6 VLPs not only elicited higher neutralizing antibody titers, ranging from 640 to 1280, but also induced higher IL-2, IL-4, IL-5, IFN-γ and TNF production, thus indicating that H5N6 VLPs may be a potential vaccine candidate for broad-spectrum H5Nx avian influenza vaccines.

High Mannose-Specific Aptamers for Broad-Spectrum Virus Inhibition and Cancer Targeting

High Mannose-Specific Aptamers for Broad-Spectrum Virus Inhibition and Cancer Targeting

Lactoferrin Can Attenuate SARS-CoV-2: An Analysis of Evidential Relations

Background: Lactoferrin (Lf ) has been shown to have antiviral action against a variety of animal and human viruses, particularly deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) viruses. This review aims to summarize the pharmacological activities that lead to the influential role of Lf against SARS-CoV-2. Methods: An all-inclusive search of published articles was carried out to focus on publications related to Lf and its biological/pharmacological activities using various literature databases, including the scientific databases Science Direct, Scopus, Web of Science, PubMed, Google Scholar, Google, EMBASE, and Scientific Information (SID). Results: By acting on cell targets, Lf prevents viral attachment, surface accumulation on the host cell, and virus penetration. Lf has shown high antiviral effectiveness across a broad spectrum of viruses, suggesting that it might be used to cure and prevent severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Lf can also attach to viral particles directly, such as hepatitis C virus (HCV), and steer them away from certain sites. LF has a powerful attraction for iron, with a constant of approximately 1020. Lf capacity to link iron relies on the existence of (minute amounts of ) bicarbonate. The bacteriostatic effect of Lf is due to its capability to come together with free iron, which is one of the ingredients necessary for bacterial development. Lf located in neutrophil secondary granules is essential for host defense. Conclusion: Researchers confirmed that Lf activates natural killer (NK) cells in a study. Lf has been shown in certain studies to prevent patronization in pseudovirus severe acute respiratory syndrome (SARS) cases that leads to attenuation of SARS-CoV-2. Lf may decrease inflammation induced by microbial exposure and directly reduce bacterial growth. It is concluded that Lf possesses antibacterial, immunomodulatory, anticancer, antiviral, cytoprotective, and anti-inflammatory activities, which ultimately act as an antiviral against SARS-CoV-2 via various mechanisms.

Characterization of a monoclonal antibody against the hemagglutinin stem of H7N9 subtype avian influenza virus

The conserved hemagglutinin (HA) stem region of avian influenza virus (AIV) is an important target for designing broad-spectrum vaccines, therapeutic antibodies and diagnostic reagents. Previously, we obtained a monoclonal antibody (mAb) (5D3-1B5) which was reactive with the HA stem epitope (aa 428-452) of H7N9 subtype AIV. To systematically characterize the mAb, we determined the antibody titers, including the HA-binding IgG, hemagglutination-inhibition (HI) and virus neutralizing (VN) titers. In addition, the antigenic epitope recognized by the antibody as well as the sequence and structure of the antibody variable region (VR) were also determined. Moreover, we evaluated the cross-reactivity of the antibody with influenza virus strains of different subtypes. The results showed that the 5D3-1B5 antibody had undetectable HI and VN activities against H7N9 virus, whereas it exhibited strong reactivity with the HA protein. Using the peptide-based enzyme-linked immunosorbent assay and biopanning with a phage-displayed random peptide library, a motif with the core sequence (431W-433Y-437L) in the C-helix domain in the HA stem was identified as the epitope recognized by 5D3-1B5. Moreover, the mAb failed to react with the mutant H7N9 virus which contains mutations in the epitope. The VR of the antibody was sequenced and the complementarity determining regions in the VR of the light and heavy chains were determined. Structural modeling and molecular docking analysis of the VR verified specific binding between the antibody and the C-helix domain of the HA stem. Notably, 5D3-1B5 showed a broad cross-reactivity with influenza virus strains of different subtypes belonging to groups 1 and 2. In conclusion, 5D3-1B5 antibody is a promising candidate in terms of the development of broad-spectrum virus diagnostic reagents and therapeutic antibodies. Our findings also provided new information for understanding the epitope characteristics of the HA protein of H7N9 subtype AIV.

MxA: a broadly acting effector of interferon-induced human innate immunity

The Human MxA protein belongs to the dynamin superfamily of large GTPases and plays a vital role in human immunity against a broad spectrum of viruses. Evasion from MxA restriction accounts for the zoonotic transmission of many pathogenic viruses. In addition to its antiviral activity, MxA has also been implicated as an inhibitor against tumor cell motility and invasion. Over the past few decades, many advances have been made in elucidating the molecular mechanisms of MxA-mediated autoimmunity, including the determination of MxA structures at high resolutions. Together, they provide exciting insights into the antiviral function of MxA, laying a solid foundation for antiviral drug development and pandemic virus infection control, and also shed light on the development of novel approaches for the prevention and treatment against cancer metastasis.