key: cord-0971133-94z3k366 authors: Hemachudha, Pasin; Petcharat, Sininat; Ampoot, Weenassarin; Ponpinit, Teerada; Paitoonpong, Leilani; Hemachudha, Thiravat title: Genetic variations from successive whole genome sequencing during COVID-19 treatment in five individuals date: 2022-01-11 journal: New Microbes New Infect DOI: 10.1016/j.nmni.2022.100950 sha: 9bf911782f6f458e8fbac4673f59fec47ba4c9fc doc_id: 971133 cord_uid: 94z3k366 We report multiple single nucleotide polymorphism taken at different time interval during treatment of COVID-19. Gene sequencing showed mutation within ORF1b at position P314L. Mutation at this point has been shown to impose structural remodelling that increases the affinity for remdesivir binding and may also affect binding affinity for favipiravir. On this outbreak, we observed many more patients progressing to severe pneumonia with 23 successive nasopharyngeal and throat (NP and T) swabs showing reduced cycle threshold (CT) from 24 RT-PCR reflecting higher viral load after five days of Favipiravir. Patient who progresses while on 25 favipiravir will be re-swab and if CT remains low, they will be switched to remdesivir, a ribonucleotide 26 analogue and increase in dexamethasone. As a result, many patients were showing improvement in 27 pneumonia with higher CT value. This approach is necessary due to limited supply of remdesivir in 28 Thailand. To explain this differing response to antiviral, nasopharyngeal and throat swab samples from individuals. Mutation at this point has been shown to impose structural remodelling that increases 53 the affinity for remdesivir binding (4, 5) . Further mutation will occur in every replicative cycle due to 54 its RNA structure and the pandemic will provide a platform for rapid turnover and accelerated 55 mutations. Constant global systematic surveillance of significant mutation is urgently needed to study 56 the viral behaviors and assists in epidemiological data gathering. The coding capacity of SARS-CoV-65 2 More Favourable Binding to SARS-CoV-2 RNA Dependent RNA Polymerase Mutant P323L Than 68 Identification of novel mutations in RNA-dependent RNA N:S255A N:G204R N:G204R N:G204R ORF1a:T1001I N:L139F N:R203M N:G204R N:G204R N:G204R N:R203K ORF1a:T1001I N:S235F N:S235F N:S235F ORF1a:A1708D N:R203M N:D377Y N:Q229H N:Q229H ORF1a:A565V N:G204R ORF1a:A1708D ORF1a:T1001I ORF1a:A1708D ORF1a:T1001I ORF1a:I2230T N:D377Y N:R385K N:S235F N:S235F ORF1a:S944L ORF1a:A565V ORF1a:I2230T ORF1a:A1708D ORF1a:I2230T ORF1a:A1708D ORF1b:P314L N:R385K ORF1a:P309L ORF1a:T1001I ORF1a:T1001I ORF1a:T1001I ORF1a:S944L ORF1a:A2249V ORF1a:I2230T ORF1b:P314L ORF1a:I2230T ORF3a:G254* ORF1a:P309L ORF1a:A3209V ORF1a:Q1129R ORF1a:Q1129R ORF1a:A1708D ORF1a:T1001I ORF1b:P314L ORF1a:A2249V ORF3a:G254* ORF1b:P314L ORF8:Q27* ORF1a:P1640L ORF1a:V3718A ORF1a:A1708D ORF1a:A1708D ORF1a:I2230T ORF1a:A1708D ORF3a:G254* ORF1b:P314L ORF8:Q27* ORF3a:G254* ORF8:R52I ORF1a:A3209V ORF1b:P314L ORF1a:I2230T ORF1a:I2230T ORF1b:P314L ORF1a:I2230T ORF8:Q27* ORF3a:G254* ORF8:R52I ORF8:Q27* ORF8:Y73C ORF1a:V3718A ORF1b:G662S ORF3a:G254* ORF1b:P314L ORF3a:G254* ORF3a:G254* ORF8:R52I ORF8:Q27* ORF8:Y73C ORF8:R52I S:L5F ORF1b:P314L ORF1b:P1000L ORF8:Q27* ORF3a:G254* ORF8:Q27* ORF8:Q27* ORF8:Y73C ORF8:R52I S:L5F ORF8:Y73C S:A570D ORF1b:G662S ORF1b:H2285Y ORF8:R52I ORF8:R52I ORF8:R52I ORF8:R52I S:N501Y ORF8:Y73C S:A570D S:L5F S:D614G ORF1b:P1000L ORF3a:S26L ORF8:Y73C ORF8:Y73C ORF8:Y73C ORF8:K68* S:A570D S:A570D S:D614G S:N501Y S:P681H ORF1b:H2285Y ORF7a:V82A S:N501Y S:N501Y S:A570D ORF8:Y73C S:D614G S:D614G S:P681H S:A570D S:T716I ORF3a:S26L ORF7a:T120I S:A570D S:A570D S:D614G S:A570D S:P681H S ORF1a:S3675-ORF1a:S3675-ORF1a:S3675-ORF1a:S3675-ORF1a:S3675-ORF8:D119-ORF8:D119-ORF1a:S3675-ORF1a:S3675-ORF1a:S3675-ORF1a:S3675-ORF1a:G3676-ORF1a:G3676-ORF1a:G3676-ORF1a:G3676-ORF1a:G3676-ORF8:F120-ORF8:F120-ORF1a:G3676-ORF1a:G3676-ORF1a:G3676-ORF1a:G3676-ORF1a:F3677-ORF1a:F3677-ORF1a:F3677-ORF1a:F3677-ORF1a:F3677-S:E156-S:E156-ORF1a:F3677-ORF1a:F3677-ORF1a:F3677-ORF1a