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. 2020 Jun 30;107:383–416. doi: 10.1016/bs.aivir.2020.06.003

Table 2.

Summary of the application of reverse genetics in live attenuated vaccines of different members of Coronaviridae.

Coronaviridae Virus Mutation sites Evaluation Reference
Alphacoronavirus PEDV nsp15: H262A Attenuation Deng et al. (2019)
nsp16: KDKE/AAAA Attenuation and protective immunity against parental strain infection Hou et al. (2019a)
S: ΔYxxΦEKVHVQ of the S protein or Δ197aa ΔYxxΦEKVHVQ: attenuation
Δ197aa: attenuation, reduces the protection
Hou et al., 2017, Hou et al., 2019b
ORF3: ΔORF3 Attenuation Beall et al. (2016)
Betacoronavirus MERS-CoV Deletion: ΔE,3, 4a, 4b, and 5 None Almazan et al. (2013)
nsp16: D130A Attenuation and protection against a lethal MERS-CoV challenge Menachery et al. (2017a)
MHV nsp1: Δ99 nts (829–927 nt) or Δ27 nts between nts 780–808 (LLRKxGxKG) Δ99 nts: attenuation and protection of mice from homologous and heterologous viral infections
Δ27 nts: attenuation and protection against challenge with WT MHV-A59 virus
Lei et al. (2013) and Zust et al. (2007)
nsp2: Δnsp2 None Graham et al. (2005)
nsp3: V787S or N1347A V787S: reduced pathogenesis and protection against challenge with WT virus
N1347A: reductions in lethality and weight loss
Fehr et al. (2015) and Mielech et al. (2015)
nsp5: T26I/D65G Attenuation Deng et al. (2014)
nsp15: H262A Attenuation and protective immunity against WT virus infection Deng et al. (2017)
SARS-CoV nsp1: ΔLLRKNGNKG (121–129aa)ΔEDYEQNWNTKH(154–164aa) No significant weight loss and 100% survived the challenge Jimenez-Guardeno et al. (2015)
nsp2: Δnsp2 None Graham et al. (2005)
nsp3: N1040A Attenuation Fehr et al. (2016)
nsp14: D90A/E92A Reductions in weight loss and lung titer Graham et al. (2012)
nsp16: D130A Attenuation in a variety of pathogenic outcomes and minimal weight loss Menachery et al. (2014)
E: ΔPBM of the E protein Decreased lung pathology Jimenez-Guardeno et al. (2014)
Gammacoronavirus IBV Δ3ab/5ab Attenuation and protection against a homologous challenge Van Beurden et al. (2018)
Δ3ab/5ab of Beaudette and the S gene was replaced by the S gene from the M14 strain Attenuation and protection against a M14 strain challenge Van Beurden et al. (2018)
Deltacoronavirus PDCoV NS6:ΔNS6 Attenuation Zhang et al. (2020)