Topology Optimization Enables High-Q Metasurface for Color Selectivity.

Nonlocal metasurfaces, exemplified by resonant waveguide gratings (RWGs), spatially and angularly configure optical wavefronts through narrow-band resonant modes, unlike the broad-band and broad-angle responses of local metasurfaces. However, forward design techniques for RWGs remain constrained at lower efficiency. Here, we present a topology-optimized metasurface resonant waveguide grating (MRWG) composed of titanium dioxide on a glass substrate capable of operating simultaneously at red, yellow, green, and blue wavelengths. Through adjoint-based topology optimization, while considering nonlocal effects, we significantly enhance its diffraction efficiency, achieving numerical efficiencies up to 78% and Q-factors as high as 1362. Experimentally, we demonstrated efficiencies of up to 59% with a Q-factor of 93. Additionally, we applied our topology-optimized metasurface to color selectivity, producing vivid colors at 4 narrow-band wavelengths. Our investigation represents a significant advancement in metasurface technology, with potential applications in see-through optical combiners and augmented reality platforms.

The Applications of Nanopore Sequencing Technology in Animal and Human Virus Research.

In recent years, an increasing number of viruses have triggered outbreaks that pose a severe threat to both human and animal life, as well as caused substantial economic losses. It is crucial to understand the genomic structure and epidemiology of these viruses to guide effective clinical prevention and treatment strategies. Nanopore sequencing, a third-generation sequencing technology, has been widely used in genomic research since 2014. This technology offers several advantages over traditional methods and next-generation sequencing (NGS), such as the ability to generate ultra-long reads, high efficiency, real-time monitoring and analysis, portability, and the ability to directly sequence RNA or DNA molecules. As a result, it exhibits excellent applicability and flexibility in virus research, including viral detection and surveillance, genome assembly, the discovery of new variants and novel viruses, and the identification of chemical modifications. In this paper, we provide a comprehensive review of the development, principles, advantages, and applications of nanopore sequencing technology in animal and human virus research, aiming to offer fresh perspectives for future studies in this field.

Enteric coronavirus nsp2 is a virulence determinant that recruits NBR1 for autophagic targeting of TBK1 to diminish the innate immune response.

Non-structural protein 2 (nsp2) exists in all coronaviruses (CoVs), while its primary function in viral pathogenicity, is largely unclear. One such enteric CoV, porcine epidemic diarrhea virus (PEDV), causes high mortality in neonatal piglets worldwide. To determine the biological role of nsp2, we generated a PEDV mutant containing a complete nsp2 deletion (rPEDV-Δnsp2) from a highly pathogenic strain by reverse genetics, showing that nsp2 was dispensable for PEDV infection, while its deficiency reduced viral replication in vitro. Intriguingly, rPEDV-Δnsp2 was entirely avirulent in vivo, with significantly increased productions of IFNB (interferon beta) and IFN-stimulated genes (ISGs) in various intestinal tissues of challenged newborn piglets. Notably, nsp2 targets and degrades TBK1 (TANK binding kinase 1), the critical kinase in the innate immune response. Mechanistically, nsp2 induced the macroautophagy/autophagy process and recruited a selective autophagic receptor, NBR1 (NBR1 autophagy cargo receptor). NBR1 subsequently facilitated the K48-linked ubiquitination of TBK1 and delivered it for autophagosome-mediated degradation. Accordingly, the replication of rPEDV-Δnsp2 CoV was restrained by reduced autophagy and excess productions of type I IFNs and ISGs. Our data collectively define enteric CoV nsp2 as a novel virulence determinant, propose a crucial role of nsp2 in diminishing innate antiviral immunity by targeting TBK1 for NBR1-mediated selective autophagy, and pave the way to develop a new type of nsp2-based attenuated PEDV vaccine. The study also provides new insights into the prevention and treatment of other pathogenic CoVs.Abbreviations: 3-MA: 3-methyladenine; Baf A1: bafilomycin A1; CoV: coronavirus; CQ: chloroquine; dpi: days post-inoculation; DMVs: double-membrane vesicles; GABARAP: GABA type A receptor-associated protein; GFP: green fluorescent protein; GIGYF2: GRB10 interacting GYF protein 2; hpi: hours post-infection; IFA: immunofluorescence assay; IFIH1: interferon induced with helicase C domain 1; IFIT2: interferon induced protein with tetratricopeptide repeats 2; IFITM1: interferon induced transmembrane protein 1; IFNB: interferon beta; IRF3: interferon regulatory factor 3; ISGs: interferon-stimulated genes; mAb: monoclonal antibody; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAVS: mitochondrial antiviral signaling protein; NBR1: NBR1 autophagy cargo receptor; nsp2: non-structural protein 2; OAS1: 2'-5'-oligoadenylate synthetase 1; PEDV: porcine epidemic diarrhea virus; PRRs: pattern recognition receptors; RIGI: RNA sensor RIG-I; RT-qPCR: reverse transcription quantitative polymerase chain reaction; SQSTM1: sequestosome 1; TBK1: TANK binding kinase 1; TCID50: 50% tissue culture infectious doses; VSV: vesicular stomatitis virus.

Cross-species transmission and animal infection model of hepatitis E virus.

Zoonotic hepatitis E virus (HEV) infection is an emerging global public health concern, and understanding the dynamics of HEV transmission between animals and humans is crucial for public health. Animal models are critical to advancing the understanding of HEV pathogenesis, drug screening, vaccine development, and other related areas. Here, we provide an overview of recent studies investigating the cross-species transmission of HEV, and also delve into the current research and application of animal HEV infection models including non-human primates, rodents, pigs, and chickens, offering a comprehensive assessment of the advantages and disadvantages of each model. This review highlights the findings related to viral replication, shedding patterns, and immune response in these animal models, and discusses the implications for our understanding of HEV transmission to humans. These advancements in the field enhance our understanding of the biological traits and pathogenic mechanisms of HEV, offering robust support for the development of highly effective and targeted prevention and treatment strategies.

Fucoidan from Ascophyllum nodosum and Undaria pinnatifida attenuate SARS-CoV-2 infection in vitro and in vivo by suppressing ACE2 and alleviating inflammation.

The global healthcare challenge posed by COVID-19 necessitates the continuous exploration for novel antiviral agents. Fucoidans have demonstrated antiviral activity. However, the underlying structure-activity mechanism responsible for the inhibitory activity of fucoidans from Ascophyllum nodosum (FUCA) and Undaria pinnatifida (FUCU) against SARS-CoV-2 remains unclear. FUCA was characterized as a homopolymer with a backbone structure of repeating (1 â†’ 3) and (1 â†’ 4) linked α-l-fucopyranose residues, whereas FUCU was a heteropolysaccharide composed of Fuc1-3Gal1-6 repeats. Furthermore, FUCA demonstrated significantly higher anti-SARS-CoV-2 activity than FUCU (EC50: 48.66 vs 69.52 µg/mL), suggesting the degree of branching rather than sulfate content affected the antiviral activity. Additionally, FUCA exhibited a dose-dependent inhibitory effect on ACE2, surpassing the inhibitory activity of FUCU. In vitro, both FUCA and FUCU treatments downregulated the expression of pro-inflammatory cytokines (IL-6, IFN-α, IFN-γ, and TNF-α) and anti-inflammatory cytokines (IL-10 and IFN-ß) induced by viral infection. In hamsters, FUCA demonstrated greater effectiveness in attenuating lung and gastrointestinal injury and reducing ACE2 expression, compared to FUCU. Analysis of the 16S rRNA gene sequencing revealed that only FUCU partially alleviated the gut microbiota dysbiosis caused by SARS-CoV-2. Consequently, our study provides a scientific basis for considering fucoidans as poteintial prophylactic food components against SARS-CoV-2.

Functional dissection of the spike glycoprotein S1 subunit and identification of cellular cofactors for regulation of swine acute diarrhea syndrome coronavirus entry.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel porcine enteric coronavirus, and the broad interspecies infection of SADS-CoV poses a potential threat to human health. This study provides experimental evidence to dissect the roles of distinct domains within the SADS-CoV spike S1 subunit in cellular entry. Specifically, we expressed the S1 and its subdomains, S1A and S1B. Cell binding and invasion inhibition assays revealed a preference for the S1B subdomain in binding to the receptors on the cell surface, and this unknown receptor is not utilized by the porcine epidemic diarrhea virus. Nanoparticle display demonstrated hemagglutination of erythrocytes from pigs, humans, and mice, linking the S1A subdomain to the binding of sialic acid (Sia) involved in virus attachment. We successfully rescued GFP-labeled SADS-CoV (rSADS-GFP) from a recombinant cDNA clone to track viral infection. Antisera raised against S1, S1A, or S1B contained highly potent neutralizing antibodies, with anti-S1B showing better efficiency in neutralizing rSADS-GFP infection compared to anti-S1A. Furthermore, depletion of heparan sulfate (HS) by heparinase treatment or pre-incubation of rSADS-GFP with HS or constituent monosaccharides could inhibit SADS-CoV entry. Finally, we demonstrated that active furin cleavage of S glycoprotein and the presence of type II transmembrane serine protease (TMPRSS2) are essential for SADS-CoV infection. These combined observations suggest that the wide cell tropism of SADS-CoV may be related to the distribution of Sia or HS on the cell surface, whereas the S1B contains the main protein receptor binding site. Specific host proteases also play important roles in facilitating SADS-CoV entry.IMPORTANCESwine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel pathogen infecting piglet, and its unique genetic evolution characteristics and broad species tropism suggest the potential for cross-species transmission. The virus enters cells through its spike (S) glycoprotein. In this study, we identify the receptor binding domain on the C-terminal part of the S1 subunit (S1B) of SADS-CoV, whereas the sugar-binding domain located at the S1 N-terminal part of S1 (S1A). Sialic acid, heparan sulfate, and specific host proteases play essential roles in viral attachment and entry. The dissection of SADS-CoV S1 subunit's functional domains and identification of cellular entry cofactors will help to explore the receptors used by SADS-CoV, which may contribute to exploring the mechanisms behind cross-species transmission and host tropism.

Type-II IFN inhibits SARS-CoV-2 replication in human lung epithelial cells and ex vivo human lung tissues through indoleamine 2,3-dioxygenase-mediated pathways.

Interferons (IFNs) are critical for immune defense against pathogens. While type-I and -III IFNs have been reported to inhibit SARS-CoV-2 replication, the antiviral effect and mechanism of type-II IFN against SARS-CoV-2 remain largely unknown. Here, we evaluate the antiviral activity of type-II IFN (IFNγ) using human lung epithelial cells (Calu3) and ex vivo human lung tissues. In this study, we found that IFNγ suppresses SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Moreover, IFNγ treatment does not significantly modulate the expression of SARS-CoV-2 entry-related factors and induces a similar level of pro-inflammatory response in human lung tissues when compared with IFNß treatment. Mechanistically, we show that overexpression of indoleamine 2,3-dioxygenase 1 (IDO1), which is most profoundly induced by IFNγ, substantially restricts the replication of ancestral SARS-CoV-2 and the Alpha and Delta variants. Meanwhile, loss-of-function study reveals that IDO1 knockdown restores SARS-CoV-2 replication restricted by IFNγ in Calu3 cells. We further found that the treatment of l-tryptophan, a substrate of IDO1, partially rescues the IFNγ-mediated inhibitory effect on SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Collectively, these results suggest that type-II IFN potently inhibits SARS-CoV-2 replication through IDO1-mediated antiviral response.

Metasurface- and PCSEL-Based Structured Light for Monocular Depth Perception and Facial Recognition.

The novel depth-sensing system presented here revolutionizes structured light (SL) technology by employing metasurfaces and photonic crystal surface-emitting lasers (PCSELs) for efficient facial recognition in monocular depth-sensing. Unlike conventional dot projectors relying on diffractive optical elements (DOEs) and collimators, our system projects approximately 45,700 infrared dots from a compact 297-µm-dimention metasurface, drastically more spots (1.43 times) and smaller (233 times) than the DOE-based dot projector in an iPhone. With a measured field-of-view (FOV) of 158° and a 0.611° dot sampling angle, the system is lens-free and lightweight and boasts lower power consumption than vertical-cavity surface-emitting laser (VCSEL) arrays, resulting in a 5-10 times reduction in power. Utilizing a GaAs-based metasurface and a simplified optical architecture, this innovation not only addresses the drawbacks of traditional SL depth-sensing but also opens avenues for compact integration into wearable devices, offering remarkable advantages in size, power efficiency, and potential for widespread adoption.

Metasurface-driven polarization-division multiplexing of PCSEL for optical communications.

Free-space optical communications hold promising advantages, including a large bandwidth, access to license-free spectrum, high data rates, quick and simple deployment, low power consumption, and relaxed quality requirements. Nevertheless, key technical challenges remain, such as a higher transmission efficiency, a lower transmission loss, and a smaller form factor of optical systems. Here, we demonstrate the viability of circular-polarization-multiplexed multi-channel optical communication using metasurfaces alongside a photonic-crystal surface-emitting laser (PCSEL) light source at wavelength of 940 nm. Through the light manipulation with metasurface, we split the linearly polarized incidence into left and right circular polarizations with desired diffraction angles. Such orthogonal polarization states provide a paradigm of polarization division multiplexing technique for light communication. The PCSEL light source maintains a low divergence angle of about 0.373 degrees after passing through an ultra-thin metasurface without further bulky collimator or light guide, making end-to-end (E2E) and device-to-device (D2D) communications available in a compact form. Both light source and modulated polarized light exhibit a - 3 dB bandwidth over 500 MHz, with successful 1 Gbit/s transmission demonstrated in eye diagrams. Our results affirm that metasurface effectively boosts transmission capacity without compromising the light source's inherent properties. Future metasurface designs could expand channel capacity, and its integration with PCSEL monolithically holds promise for reducing interface losses, thereby enhancing efficiency.

Generation and Characterization of Monoclonal Antibodies against Swine Acute Diarrhea Syndrome Coronavirus Spike Protein.

Swine acute diarrhea syndrome coronavirus (SADS-CoV), a member of the family Coronaviridae and the genus Alphacoronavirus, primarily affects piglets under 7 days old, causing symptoms such as diarrhea, vomiting, and dehydration. It has the potential to infect human primary and passaged cells in vitro, indicating a potential risk of zoonotic transmission. In this study, we successfully generated and purified six monoclonal antibodies (mAbs) specifically targeting the spike protein of SADS-CoV, whose epitope were demonstrated specificity to the S1A or S1B region by immunofluorescence assay and enzyme-linked immunosorbent assay. Three of these mAbs were capable of neutralizing SADS-CoV infection on HeLa-R19 and A549. Furthermore, we observed that SADS-CoV induced the agglutination of erythrocytes from both humans and rats, and the hemagglutination inhibition capacity and antigen-antibody binding capacity of the antibodies were assessed. Our study reveals that mAbs specifically targeting the S1A domain demonstrated notable efficacy in suppressing the hemagglutination phenomenon induced by SADS-CoV. This finding represents the first instance of narrowing down the protein region responsible for SADS-CoV-mediated hemagglutination to the S1A domain, and reveals that the cell attachment domains S1A and S1B are the main targets of neutralizing antibodies.

Reverse genetics systems for SARS-CoV-2: Development and applications.

The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused serious harm to human health and struck a blow to global economic development. Research on SARS-CoV-2 has greatly benefited from the use of reverse genetics systems, which have been established to artificially manipulate the viral genome, generating recombinant and reporter infectious viruses or biosafety level 2 (BSL-2)-adapted non-infectious replicons with desired modifications. These tools have been instrumental in studying the molecular biological characteristics of the virus, investigating antiviral therapeutics, and facilitating the development of attenuated vaccine candidates. Here, we review the construction strategies, development, and applications of reverse genetics systems for SARS-CoV-2, which may be applied to other CoVs as well.

Enrichment of anchoring sites by introducing supramolecular halogen bonds for the efficient perovskite nanocrystal LEDs.

Considering the multi-functionalization of ligands, it is crucial for ligand molecular design to reveal the landscape of anchoring sites. Here, a typical triphenylphosphine (TPP) ligand was employed to explore its effect on the surface of CsPbI3 perovskite nanocrystals (PNCs). Except for the conventionally considered P-Pb coordination, an P-I supramolecular halogen bonding was also found on the NC surface. The coexistence of the above two types of bonding significantly increased the formation energy of iodine vacancy defects and improved the photoluminescence quantum yield of PNCs up to 93%. Meanwhile, the direct interaction of P and I enhanced the stability of the Pb-I octahedra and dramatically inhibited the migration of I ions. Furthermore, the introduction of additional benzene rings (2-(Diphenylphosphino)-biphenyl (DPB)) increased the delocalized properties of the PNC surface and significantly improved the charge transport of the PNCs. As a result, the DPB passivated CsPbI3 NCs based top-emitting LEDs exhibite a peak external quantum efficiency (EQE) of 22.8%, a maximum luminance of 15, 204 cd m-2, and an extremely low-efficiency roll-off of 2.6% at the current density of 500 mA cm-2.

Design of high-efficiency and large-angle homo-metagratings for light source integration.

Meta-optics integrated with light sources has gained significant attention. However, most focused on the efficiency of metasurfaces themselves, rather than the efficiency of integration. To design highly efficient beam deflection, we develop a scheme of homo-metagrating, involving the same material for meta-atoms, substrate, and top layer of the laser, to achieve near-unity power from light-emitting to metasurfaces. We utilize three degrees of freedom: overall add-on phase, parameters of meta-atoms in a period, and lattice arrangement. The overall efficiency of homo-metagratings is higher than that of hetero-metagratings. We believe our approach is capable of being implemented in various ultracompact optic systems.

Compact structured light generation based on meta-hologram PCSEL integration.

Metasurfaces, a catalog of optical components, offer numerous novel functions on demand. They have been integrated with vertical cavity surface-emitting lasers (VCSELs) in previous studies. However, the performance has been limited by the features of the VCSELs such as low output power and large divergence angle. Although the solution of the module of VCSEL array could solve these issues, the practical application is limited by extra lens and large size. In this study, we experimentally demonstrate reconstruction of a holographic images using a compact integration of a photonic crystal surface-emitting laser and metasurface holograms designed for structured light generation. This research showcases the flexible design capabilities of metasurfaces, high output power (on the order of milliwatts), and the ability to produce well-uniformed images with a wide field of view without the need for a collection lens, making it suitable for 3D imaging and sensing.

Production of singlet oxygen from photosensitizer erythrosine for facile inactivation of coronavirus on mask.

The global health crisis caused by the COVID-19 pandemic has led to a surge in demand and use of personal protective equipment (PPE) such as masks, putting great pressure on social production and the environment.It is urgent to find an efficient and non-destructive disinfection method for the safe reuse of PPE. This study proposes a PPE disinfection method that uses erythrosine, a U.S. Food and Drug Administration-approved food dye, as photosensitizer to produce singlet oxygen for virus inactivation, and indicates the completion of disinfection by its photobleaching color change.After spraying 100 µL of 10 µM erythrosine on the surface of the mask for 3 times and light exposure for 25 min, the titer of coronavirus decreased by more than 99.999%, and the color of erythrosine on the mask surface disappeared. In addition, the structure of the mask was intact and the filtration efficiency was maintained at > 95% after 10 cycles of erythrosine treatment.Therefore, this disinfection method can provide at least 10 cycles of reuse with the advantages of high safety and convenient, and the completion of disinfection can be indicated by its photobleaching, which is suitable for hospitals and daily life to reduce the consumption of PPE.

Comparative analysis of newly identified rodent arteriviruses and porcine reproductive and respiratory syndrome virus to characterize their evolutionary relationships.

Porcine reproductive and respiratory syndrome virus (PRRSV) has caused huge economic losses for the global pig industry, but its origins and evolution remain a mystery. In 2018, the genome sequences of seven arteriviruses isolated from rodents were determined, and here we publish new analysis showing that they may be ancestors of PRRSV. The sequence similarity of these viruses to PRRSV was ~60%, with shared genome organization and other characteristics, such as slippery sequences and C-rich motifs in nsp2, and a transactivated protein sequence in nsp1ß. Codon usage basis analysis showed that PRRSV was closer to these rodent arteriviruses than lactate dehydrogenase-elevating virus (LDV) and they were both under pressure of natural selection. Evolutionary analysis revealed that four of the rodent arteriviruses shared the same genus with PRRSV, and were more closely related to PRRSV-2 than PRRSV-1. In addition to this, they all appeared earlier than PRRSV according to evolutionary modeling, and we speculate that they represent an intermediate step in the origin of PRRSV by arterivirus transmission from rodents to swine. Our in-depth analysis furthers our understanding of arteriviruses, and will serve as the basis for subsequent exploration of the evolution of PRRSV and other arteriviruses.

Heat shock protein 90 facilitates SARS-CoV-2 structural protein-mediated virion assembly and promotes virus-induced pyroptosis.

Inhibition of heat shock protein 90 (Hsp90), a prominent molecular chaperone, effectively limits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but little is known about any interaction between Hsp90 and SARS-CoV-2 proteins. Here, we systematically analyzed the effects of the chaperone isoforms Hsp90α and Hsp90ß on individual SARS-CoV-2 viral proteins. Five SARS-CoV-2 proteins, namely nucleocapsid (N), membrane (M), and accessory proteins Orf3, Orf7a, and Orf7b were found to be novel clients of Hsp90ß in particular. Pharmacological inhibition of Hsp90 with 17-DMAG results in N protein proteasome-dependent degradation. Hsp90 depletion-induced N protein degradation is independent of CHIP, a ubiquitin E3 ligase previously identified for Hsp90 client proteins, but alleviated by FBXO10, an E3 ligase identified by subsequent siRNA screening. We also provide evidence that Hsp90 depletion may suppress SARS-CoV-2 assembly partially through induced M or N degradation. Additionally, we found that GSDMD-mediated pyroptotic cell death triggered by SARS-CoV-2 was mitigated by inhibition of Hsp90. These findings collectively highlight a beneficial role for targeting of Hsp90 during SARS-CoV-2 infection, directly inhibiting virion production and reducing inflammatory injury by preventing the pyroptosis that contributes to severe SARS-CoV-2 disease.

The origin and evolution of emerged swine acute diarrhea syndrome coronavirus with zoonotic potential.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered alphacoronavirus with zoonotic potential that causes diarrhea and vomiting mainly in piglets. Having emerged suddenly in 2017, the prevailing opinion is that the virus originated from HKU2, an alphacoronavirus whose primary host is bats, and at some unknown point achieved interspecies transmission via some intermediate. Here, we further explore the evolutionary history and possible cross-species transmission event for SADS-CoV. Coevolutionary analysis demonstrated that HKU2 may have achieved host switch via SADS-related (SADSr)-CoV, which was isolated from the genus Rhinolophus in 2017. SADS-CoV, HKU2, and SADSr-CoV share similar codon usage patterns and showed a lower tendency to use CpG, which may reflect a method of immune escape. The analyses of virus-host coevolution and recombination support SADSr-CoV is the direct source of SADS-CoV that may have undergone recombination events during its formation. Structure-based spike glycoprotein variance analysis revealed a more nuanced evolutionary pathway to receptor recognition for host switch. We did not find a possible positive selection site, and the dN/dS of the S gene was only 0.29, which indicates that the current SADS-CoV is slowly evolving. These results provide new insights that may help predict future cross-species transmission, and possibly surveil future zoonotic outbreaks and associated public health emergencies.

Role of heat shock protein 90 as an antiviral target for swine enteric coronaviruses.

A variety of swine enteric coronaviruses (SECoVs) have emerged and are prevalent in pig populations, including porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome (SADS)-CoV, a newly identified bat-origin CoV with zoonotic potential. Unfortunately, available traditional, inactivated and attenuated SECoV vaccines are of limited efficacy against the variants currently circulating in most pig populations. In this study, we evaluated the role of host factor heat shock protein 90 (Hsp90) as an antiviral target against SECoVs, exemplified by SADS-CoV. Pharmacological inhibition of Hsp90 diminished SADS-CoV replication significantly in porcine and human cell lines, and also decreased replication of SADS-CoV in a porcine intestinal enteroid model. Further mechanistic experiments revealed that both porcine and human isoforms of Hsp90 interact with the SADS-CoV nucleocapsid (N) protein, and inhibition of Hsp90 resulted in autophagic degradation of N protein. Moreover, we linked Hsp90 to virus-induced cellular pyroptosis, as SADS-CoV was found to trigger caspase-1/gasdermin-d-mediated pyroptotic cell death, which was mitigated by inhibition of Hsp90. Finally, we demonstrated that Hsp90 also associated with N proteins and was involved in propagation of PEDV, PDCoV and TGEV. This study thus extends our understanding of immune responses to SADS-CoV infection and offers a new potential therapeutic option against four SECoVs.