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1.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-334805

ABSTRACT

Omicron sub-lineage BA.2 has rapidly surged globally, accounting for over 60% of recent SARS-CoV-2 infections. Newly acquired RBD mutations and high transmission advantage over BA.1 urge the investigation of BA.2's immune evasion capability. Here, we show that BA.2 causes strong neutralization resistance, comparable to BA.1, in vaccinated individuals' plasma. However, BA.2 displays more severe antibody evasion in BA.1 convalescents, and most prominently, in vaccinated SARS convalescents' plasma, suggesting a substantial antigenicity difference between BA.2 and BA.1. To specify, we determined the escaping mutation profiles1,2 of 714 SARS-CoV-2 RBD neutralizing antibodies, including 241 broad sarbecovirus neutralizing antibodies isolated from SARS convalescents, and measured their neutralization efficacy against BA.1, BA.1.1, BA.2. Importantly, BA.2 specifically induces large-scale escape of BA.1/BA.1.1effective broad sarbecovirus neutralizing antibodies via novel mutations T376A, D405N, and R408S. These sites were highly conserved across sarbecoviruses, suggesting that Omicron BA.2 arose from immune pressure selection instead of zoonotic spillover. Moreover, BA.2 reduces the efficacy of S309 (Sotrovimab)3,4 and broad sarbecovirus neutralizing antibodies targeting the similar epitope region, including BD55-5840. Structural comparisons of BD55-5840 in complexes with BA.1 and BA.2 spike suggest that BA.2 could hinder antibody binding through S371F-induced N343-glycan displacement. Intriguingly, the absence of G446S mutation in BA.2 enabled a proportion of 440-449 linear epitope targeting antibodies to retain neutralizing efficacy, including COV2-2130 (Cilgavimab)5. Together, we showed that BA.2 exhibits distinct antigenicity compared to BA.1 and provided a comprehensive profile of SARS-CoV-2 antibody escaping mutations. Our study offers critical insights into the humoral immune evading mechanism of current and future variants.

2.
Jiaotong Yunshu Xitong Gongcheng Yu Xinxi/Journal of Transportation Systems Engineering and Information Technology ; 22(1):311-321, 2022.
Article in Chinese | Scopus | ID: covidwho-1771916

ABSTRACT

To assess the resistance of the shipping network of Chinese iron ore imports and the effectiveness of different safeguards, an invulnerability simulation model was established to fill the gap that traditional evaluation methods fail to consider the overall flow and nodes load state of the network. The data of a state-owned enterprise, major export ports in the world and major import ports in China were used to build the initial network. The network with different numbers of import ports was attacked in particular ways. The simulation results show that the network has a certain self-healing ability after the network is attacked, because of the adjusted ability of ship routes and redistribution of cargo load, but the network invulnerability will suddenly change after the key nodes are affected. The improvement of overload capacity has obvious marginal changes in improving network invulnerability if the overload capacity reaches a critical point, and improving the network survivability may aggravate network congestion. Therefore, it is necessary to strengthen the protection of key nodes, increase the number of import ports, and enhance the overload capacity of the ports, to enhance the invulnerability of the Chinese iron ore import shipping network under the COVID-19 and other critical events. Meanwhile, resources such as wharf yards and equipment should be reasonably allocated to prevent and deal with network congestion. Copyright © 2022 by Science Press.

3.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326764

ABSTRACT

The SARS-CoV-2 B.1.1.529 variant (Omicron) contains 15 mutations on the receptor-binding domain (RBD). How Omicron would evade RBD neutralizing antibodies (NAbs) requires immediate investigation. Here, we used high-throughput yeast display screening1,2 to determine the RBD escaping mutation profiles for 247 human anti-RBD NAbs and showed that the NAbs could be unsupervised clustered into six epitope groups (A-F), which is highly concordant with knowledge-based structural classifications3-5. Strikingly, various single mutations of Omicron could impair NAbs of different epitope groups. Specifically, NAbs in Group A-D, whose epitope overlap with ACE2-binding motif, are largely escaped by K417N, G446S, E484A, and Q493R. Group E (S309 site)6 and F (CR3022 site)7 NAbs, which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but still, a subset of NAbs are escaped by G339D, N440K, and S371L. Furthermore, Omicron pseudovirus neutralization showed that single mutation tolerating NAbs could also be escaped due to multiple synergetic mutations on their epitopes. In total, over 85% of the tested NAbs are escaped by Omicron. Regarding NAb drugs, the neutralization potency of LYCoV016/LY-CoV555, REGN10933/REGN10987, AZD1061/AZD8895, and BRII-196 were greatly reduced by Omicron, while VIR-7831 and DXP-604 still function at reduced efficacy. Together, data suggest Omicron would cause significant humoral immune evasion, while NAbs targeting the sarbecovirus conserved region remain most effective. Our results offer instructions for developing NAb drugs and vaccines against Omicron and future variants.

4.
35th AAAI Conference on Artificial Intelligence / 33rd Conference on Innovative Applications of Artificial Intelligence / 11th Symposium on Educational Advances in Artificial Intelligence ; 35:7754-7761, 2021.
Article in English | Web of Science | ID: covidwho-1381686

ABSTRACT

In the fight against the COVID-19 pandemic, many social activities have moved online;society's overwhelming reliance on the complex cyberspace makes its security more important than ever. In this paper, we propose and develop an intelligent system named Dr.HIN to protect users against the evolving Android malware attacks in the COVID-19 era and beyond. In Dr.HIN, besides app content, we propose to consider higher-level semantics and social relations among apps, developers and mobile devices to comprehensively depict Android apps;and then we introduce a structured heterogeneous information network (HIN) to model the complex relations and exploit meta-path guided strategy to learn node (i.e., app) representations from HIN. As the representations of malware could be highly entangled with benign apps in the complex ecosystem of development, it poses a new challenge of learning the latent explanatory factors hidden in the HIN embeddings to detect the evolving malware. To address this challenge, we propose to integrate domain priors generated from different views (i.e., app content, app authorship, app installation) to devise an adversarial disentangler to separate the distinct, informative factors of variations hidden in the HIN embeddings for large-scale Android malware detection. This is the first attempt of disentangled representation learning in HIN data. Promising experimental results based on real sample collections from security industry demonstrate the performance of Dr.HIN in evolving Android malware detection, by comparison with baselines and popular mobile security products.

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