Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia

Sabir, Jamal S. M.; Lam, Tommy Tsan-Yuk; Ahmed, M. A.; Li, Lifeng; Shen, Yongyi; Abo-Aba, Salah E. M.; Qureshi, M.I.; Abu-Zeid, Mohamed; Zhang, Yu; Khiyami, Mohammad A.; Alharbi, Njud S.; Hajrah, Nahid H.; Sabir, Meshaal J.; Mutwakil, Mohammed H. Z.; Kabli, Saleh A.; Alsulaimany, Faten A. S.; Obaid, Abdullah Y.; Zhou, Boping; Smith, David K.; Holmes, Edward C.; Zhu, Hua; Guan, Yi

doi:10.1126/science.aac8608

Cited by 388 publications

(453 citation statements)

References 43 publications

(8 reference statements)

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“…The CoV that causes severe acute respiratory syndrome (SARS) may have arisen from a recombination event between a bat CoV and another virus before infecting human and carnivore hosts 40 . A Middle East respiratory syndrome (MERS) CoV recombinant lineage has been dominant since December 2014 and subsequently led to human outbreaks in 2015 41 . Despite such examples in other viruses, HR is commonly thought to be rare or absent among negative-strand RNA viruses (NSRVs) 40, 42 .…”

Section: Discussionmentioning

confidence: 99%

A permanent host shift of rabies virus from Chiroptera to Carnivora associated with recombination

Ding

Sun

et al. 2017

Sci Rep

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Bat virus host shifts can result in the spread of diseases with significant effects. The rabies virus (RABV) is able to infect almost all mammals and is therefore a useful model for the study of host shift mechanisms. Carnivore RABVs originated from two historical host shifts from bat viruses. To reveal the genetic pathways by which bat RABVs changed their host tropism from bats to carnivores, we investigated the second permanent bat-to-carnivore shift resulting in two carnivore variants, known as raccoon RABV (RRV) and south-central skunk RABV (SCSKV). We found that their glycoprotein (G) genes are the result of recombination between an American bat virus and a carnivore virus. This recombination allowed the bat RABV to acquire the head of the G-protein ectodomain of the carnivore virus. This region is involved in receptor recognition and binding, response to changes in the pH microenvironment, trimerization of G proteins, and cell-to-cell transmission during the viral infection. Therefore, this recombination event may have significantly improved the variant’s adaptability to carnivores, altering its host tropism and thus leading to large-scale epidemics in striped skunk and raccoon.

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Section: Discussionmentioning

confidence: 99%

A permanent host shift of rabies virus from Chiroptera to Carnivora associated with recombination

Ding

Sun

et al. 2017

Sci Rep

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Section: -7)mentioning

confidence: 99%

“…Camels are incriminated as a potential host of the virus, and a considerable number of genomes of MERS CoV from camels were isolated and sequenced. [11][12][13] Therefore, there are two main sources of MERS CoV genomic data: humans and camels.The genetic code is comprised of 61 different codons corresponding to the standard 20 amino acids. Two of these amino acids are encoded by one codon (tyrosine (Tyr) and methionine (Met), while the other amino acids are encoded by several codons-up to 6 codons for 1 amino acid.…”

mentioning

confidence: 99%

Comparative Genomic Analysis MERS CoV Isolated from Humans and Camels with Special Reference to Virus Encoded Helicase

Alnazawi

Altaher

Kandeel

2017

Biological & Pharmaceutical Bulletin

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Middle East Respiratory Syndrome Coronavirus (MERS CoV)is a new emerging viral disease characterized by high fatality rate. Understanding MERS CoV genetic aspects and codon usage pattern is important to understand MERS CoV survival, adaptation, evolution, resistance to innate immunity, and help in finding the unique aspects of the virus for future drug discovery experiments. In this work, we provide comprehensive analysis of 238 MERS CoV full genomes comprised of human (hMERS) and camel (cMERS) isolates of the virus. MERS CoV genome shaping seems to be under compositional and mutational bias, as revealed by preference of A/T over G/C nucleotides, preferred codons, nucleotides at the third position of codons (NT3s), relative synonymous codon usage, hydropathicity (Gravy), and aromaticity (Aromo) indices. Effective number of codons (ENc) analysis reveals a general slight codon usage bias. Codon adaptation index reveals incomplete adaptation to host environment. MERS CoV showed high ability to resist the innate immune response by showing lower CpG frequencies. Neutrality evolution analysis revealed a more significant role of mutation pressure in cMERS over hMERS. Correspondence analysis revealed that MERS CoV genomes have three genetic clusters, which were distinct in their codon usage, host, and geographic distribution. Additionally, virtual screening and binding experiments were able to identify three new virus-encoded helicase binding compounds. These compounds can be used for further optimization of inhibitors.Key words codon usage; camel; Coronavirus; helicase; inhibitor Middle East Respiratory Syndrome Coronavirus (MERS CoV) is a new emerging virus infection causing lethal pneumonia and high case fatality.1-3) The infection with MERS CoV has now extended to become a global concern. 4-7)Recently, a serious outbreak of infection was recorded in South Korea and China. 8,9) MERS CoV is a single stranded RNA virus with a relatively large genome of ca. 30 kb.10) The virus was firstly isolated from humans. Currently there is still much debate in confirming the potential hosts and mode of transmission of the virus. Camels are incriminated as a potential host of the virus, and a considerable number of genomes of MERS CoV from camels were isolated and sequenced. [11][12][13] Therefore, there are two main sources of MERS CoV genomic data: humans and camels.The genetic code is comprised of 61 different codons corresponding to the standard 20 amino acids. Two of these amino acids are encoded by one codon (tyrosine (Tyr) and methionine (Met), while the other amino acids are encoded by several codons-up to 6 codons for 1 amino acid. Therefore, alternative codons present within 1 amino acid production codes are called synonymous codons.14) Codon bias infers the preference of one synonymous codon over the other, and may be over-represented to indicate overuse of a certain codon or rare codons that are rarely used for a certain gene. There are two main forces affecting the composition of a certain genome as well as codon usage...

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“…As it has been demonstrated that MERS-CoV underwent evolution during the 2012–2015 outbreaks (Cotten et al, 2013; Sabir et al., 2016), we evaluated the hMS-1 cross-neutralizing activity against these MERS-CoV emergent strains. hMS-1 recognized three key residues (neutralizing epitopes) of MERS-CoV RBD all of which were highly conserved during MERS-CoV evolution, leading to the hypothesis that hMS-1 might be effective in combatting the infections of different MERS-CoV emerging isolates.…”

Section: Discussionmentioning

confidence: 99%

Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection

et al. 2016

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Middle East respiratory syndrome coronavirus (MERS-CoV) is continuously spreading and causing severe and fatal acute respiratory disease in humans. Prophylactic and therapeutic strategies are therefore urgently needed to control MERS-CoV infection. Here, we generated a humanized monoclonal antibody (mAb), designated hMS-1, which targeted the MERS-CoV receptor-binding domain (RBD) with high affinity. hMS-1 significantly blocked MERS-CoV RBD binding to its viral receptor, human dipeptidyl peptidase 4 (hDPP4), potently neutralized infection by a prototype MERS-CoV, and effectively cross-neutralized evolved MERS-CoV isolates through recognizing highly conserved RBD epitopes. Notably, single-dose treatment with hMS-1 completely protected hDPP4 transgenic (hDPP4-Tg) mice from lethal infection with MERS-CoV. Taken together, our data suggest that hMS-1 might be developed as an effective immunotherapeutic agent to treat patients infected with MERS-CoV, particularly in emergent cases.

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Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia

Cited by 388 publications

References 43 publications

A permanent host shift of rabies virus from Chiroptera to Carnivora associated with recombination

A permanent host shift of rabies virus from Chiroptera to Carnivora associated with recombination

Comparative Genomic Analysis MERS CoV Isolated from Humans and Camels with Special Reference to Virus Encoded Helicase

Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection

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