Abstract
The genetic diversity of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) in several countries sums up to worldwide genetic diversity. In this present study, variations in terms of missense mutations among the SARS-CoV2 genomes from 128 Indian patients, as of May 2020, are accounted and thereby some key findings with some hypotheses were made. These mutations across various genes of these genomes show wide genetic variations in sequence and rapid evolution of SARS-CoV2 virus. The presence of unique mutations in the studied SARS-CoV2 genomes may led to their attenuation. Few Genes such as ORF6, ORF10 are free from any mutations in the Indian context of 339 genomes observed as of 14th July 2020. Further, E protein contains only one mutation. This may suggest that designing a therapeutic approach against ORF6, ORF10 and E genes may have a beneficial effect in controlling COVID-19 pandemic especially in India.
Keywords: Indian patients, Therapeutic target, SARS-CoV2 genomes, Missense mutations and genetic variations
Highlights
-
•
Variations in terms of missense mutations among the SARSCoV2 genomes from 128 Indian patients, as of May 2020, are accounted and thereby some key findings with some hypotheses were made.
-
•
The presence of unique mutations in the studied SARS-CoV2 genomes has led to their attenuation. Few Genes such as ORF6, ORF10 are absolutely free from any mutations in the Indian context of 339 genomes observed as of 14th July 2020. Further, E protein contains only one mutation.
-
•
This may suggest that designing a therapeutic approach against ORF6, ORF10 and E genes may have a beneficial effect in controlling COVID-19 pandemic especially in India.
1. The study
The pandemic of COVID-19, caused by the RNA coronavirus SARS-CoV2 has spread over 200 countries and infected millions of people worldwide [1,2]. The rate of mutation of RNA viruses is much higher than that of their hosts [3,4]. The rapid spread of COVID-19 across various countries opens an intriguing question whether the variations in genome sequences of the novel coronavirus are contributing to the variation of infection and mortality rate [5,6]. Having this question in mind, with the reference to the Wuhan based genome NC_045512, missense mutations were identified in the SARS-CoV2 genomes of the COVID-19 affected Indian patients. This study of mutations in the SARS-CoV2 genomes of 128 COVID-19 affected Indian patients has been carried out. Various mutations over the proteins of SARS-CoV2 genomes are presented in the articles [7,8,9,10,11,12,13]. A comprehensive list of patients with other associated details are presented in the Table 1 . It is to be noted that most of these 128 patients were infected in Europe and USA and came back to India. Some of them were infected from neighbour Indian patients.
Table 1.
List of 128 SARS-CoV2 genomes from Indian patients with their respective locations and date of collection of the sample.
| Accession | Geo_Location | Collection_Date | Accession | Geo_Location | Collection_Date | Accession | Geo_Location | Collection_Date |
|---|---|---|---|---|---|---|---|---|
| MT509494 | Vadodara | 2020-05-03 | MT496981 | Ahmedabad | 2020-05-03 | MT467252 | Ahmedabad | 2020-04-29 |
| MT509495 | Kodinar | 2020-05-10 | MT496982 | Ahmedabad | 2020-05-03 | MT467253 | Ahmedabad | 2020-04-29 |
| MT509496 | Botad | 2020-05-09 | MT496983 | Ahmedabad | 2020-05-05 | MT467254 | Ahmedabad | 2020-04-29 |
| MT509497 | Una | 2020-05-11 | MT496984 | Ahmedabad | 2020-05-03 | MT467255 | Ahmedabad | 2020-04-30 |
| MT509498 | Jamnagar | 2020-05-09 | MT496985 | Ahmedabad | 2020-05-05 | MT467256 | Ahmedabad | 2020-04-29 |
| MT509499 | Jamnagar | 2020-05-07 | MT496986 | Ahmedabad | 2020-05-05 | MT467257 | Ahmedabad | 2020-04-30 |
| MT509500 | Dahod | 2020-05-03 | MT496987 | Ahmedabad | 2020-05-04 | MT467258 | Ahmedabad | 2020-04-29 |
| MT509501 | Jamnagar | 2020-05-06 | MT496988 | Ahmedabad | 2020-05-03 | MT467259 | Prantij | 2020-05-02 |
| MT509502 | Jamnagar | 2020-05-10 | MT496989 | Ahmedabad | 2020-05-03 | MT467260 | Prantij | 2020-05-02 |
| MT509503 | Junagadh | 2020-05-09 | MT496990 | Gandhinagar | 2020-04-29 | MT467261 | Modasa | 2020-05-04 |
| MT509504 | Rajkot | 2020-05-06 | MT496991 | Gandhinagar | 2020-04-27 | MT467262 | Modasa | 2020-05-04 |
| MT509505 | Ahmedabad | 2020-04-11 | MT496992 | Ahmedabad | 2020-05-03 | MT467263 | Dhansura | 2020-05-04 |
| MT509506 | Rajkot | 2020-04-27 | MT496993 | Gandhinagar | 2020-04-29 | MT457402 | Hyderabad | 2020-03-24 |
| MT509507 | Una | 2020-05-10 | MT496994 | Gandhinagar | 2020-04-29 | MT457403 | Hyderabad | 2020-03-25 |
| MT509508 | Jamnagar | 2020-05-05 | MT496995 | Gandhinagar | 2020-04-29 | MT451874 | Surat | 2020-04-24 |
| MT509509 | Ahmedabad | 2020-04-11 | MT496996 | Gandhinagar | 2020-05-02 | MT451876 | Surat | 2020-04-26 |
| MT509510 | Una | 2020-05-10 | MT496997 | Gandhinagar | 2020-04-29 | MT451877 | Surat | 2020-04-26 |
| MT509511 | Rajkot | 2020-04-28 | MT483553 | Modasa | 2020-05-05 | MT451878 | Surat | 2020-04-27 |
| MT509512 | Dahod | 2020-05-01 | MT483554 | Modasa | 2020-05-05 | MT451880 | Surat | 2020-04-26 |
| MT481895 | Ahmedabad | 2020-05-03 | MT483555 | Modasa | 2020-05-05 | MT451881 | Ahmedabad | 2020-04-26 |
| MT481896 | Ahmedabad | 2020-05-03 | MT483556 | Modasa | 2020-05-05 | MT451882 | Ahmedabad | 2020-04-26 |
| MT481897 | Modasa | 2020-05-05 | MT483557 | Modasa | 2020-05-05 | MT451883 | Ahmedabad | 2020-04-26 |
| MT481898 | Himatnagar | 2020-05-05 | MT483558 | Modasa | 2020-05-05 | MT451884 | Ahmedabad | 2020-04-26 |
| MT481899 | Modasa | 2020-05-05 | MT483559 | Prantij | 2020-05-05 | MT451885 | Ahmedabad | 2020-04-26 |
| MT481900 | Gandhinagar | 2020-04-28 | MT483560 | Modasa | 2020-05-05 | MT451886 | Ahmedabad | 2020-04-26 |
| MT481901 | Dahegam | 2020-04-28 | MT483702 | Modasa | 2020-05-05 | MT451887 | Ahmedabad | 2020-04-26 |
| MT481902 | Dahegam | 2020-05-03 | MT477885 | India⁎ | 2020-03-25 | MT451888 | Ahmedabad | 2020-04-26 |
| MT481903 | Dahegam | 2020-05-03 | MT467237 | Ahmedabad | 2020-04-26 | MT451889 | Ahmedabad | 2020-04-26 |
| MT481904 | Gandhinagar | 2020-04-25 | MT467238 | Ahmedabad | 2020-04-29 | MT451890 | Ahmedabad | 2020-04-26 |
| MT481905 | Gandhinagar | 2020-05-02 | MT467239 | Ahmedabad | 2020-04-26 | MT435079 | Ahmedabad | 2020-04-13 |
| MT481906 | Gandhinagar | 2020-04-27 | MT467240 | Ahmedabad | 2020-04-30 | MT435080 | Ahmedabad | 2020-04-13 |
| MT481907 | Gandhinagar | 2020-04-26 | MT467241 | Ahmedabad | 2020-04-26 | MT435081 | Ahmedabad | 2020-04-13 |
| MT481908 | Mansa | 2020-04-28 | MT467242 | Ahmedabad | 2020-04-29 | MT435082 | Ahmedabad | 2020-04-13 |
| MT481909 | Modasa | 2020-05-05 | MT467243 | Ahmedabad | 2020-04-30 | MT435083 | Ahmedabad | 2020-04-07 |
| MT496972 | Ahmedabad | 2020-04-29 | MT467244 | Ahmedabad | 2020-04-30 | MT435084 | Ahmedabad | 2020-04-14 |
| MT496973 | Ahmedabad | 2020-04-29 | MT467245 | Ahmedabad | 2020-04-29 | MT435085 | Gandhinagar | 2020-04-22 |
| MT496974 | Ahmedabad | 2020-04-29 | MT467246 | Ahmedabad | 2020-04-29 | MT435086 | Mansa | 2020-04-21 |
| MT496975 | Ahmedabad | 2020-04-29 | MT467247 | Ahmedabad | 2020-04-29 | MT415320 | India⁎ | 2020-03-01 |
| MT496976 | Ahmedabad | 2020-05-03 | MT467248 | Ahmedabad | 2020-04-29 | MT415321 | India⁎ | 2020-03-11 |
| MT496977 | Ahmedabad | 2020-05-03 | MT467249 | Ahmedabad | 2020-04-29 | MT415322 | India⁎ | 2020-03-16 |
| MT496979 | Ahmedabad | 2020-05-05 | MT467250 | Ahmedabad | 2020-04-29 | MT415323 | India⁎ | 2020-03-20 |
| MT496980 | Ahmedabad | 2020-05-03 | MT467251 | Ahmedabad | 2020-04-29 | MT358637 | Rajkot | 2020-04-05 |
| MT012098 | Kerala State | 2020-01-27 | ||||||
| MT050493 | Kerala State | 2020-01-31 |
No specific name of the state/city of India is mentioned in the NCBI database.
The following Table 2, Table 3, Table 4, Table 5 adumbrate all the missense mutations along with silent mutations across the 128 virus genomes from Indian COVID-19 affected patients.
Table 2.
Missense and silent mutations in the entire genome of SARS-CoV2 from Indian patients.
| Virus Genome ID | Location | Missense and silent mutations | Genomic regions | Missense mutation |
|---|---|---|---|---|
| MT415321 | India | F(924)F, P(4715)L, G(614)G | ORF1 (2), S (1) | 1 |
| MT451878 | Surat | F(5251)F, Y(789)Y, P(13)L | ORF1 (5), S (2) | 1 |
| MT481909 | Modasa | F(924)F, Q(57)H, Y(71)Y | ORF1(1), ORF3a(1), M(1) | 1 |
| MT467257 | Ahmedabad | F(924)F, P(4715)L, D(614)G | ORF1(2), S(1) | 2 |
| MT451884 | Ahmedabad | F(924)F, P(4715)L, K(4803)K, D(614)G | ORF1(3), S(1) | 2 |
| MT467244 | Ahmedabad | F(924)F, P(4715)L, K(4803)K, D(614)G | ORF1(3), S(1) | 2 |
| MT415320 | India | N(5020)N, G(5074)G, Y(28)H, N(856)N, P(344)S | ORF1(3), S(2), N(1) | 2 |
| MT435084 | Ahmedabad | F(924)F, P(4715)L, D(614)G | ORF1(4), S(1) | 2 |
| MT435079 | Ahmedabad | F(924)F, P(4715)L, D(614)G | ORF1(9), S(1) | 2 |
| MT451883 | Ahmedabad | P(4715)L, K(4803)K, D(614)G | ORF(9), S(1) | 2 |
| MT496990 | Gandhinagar | F(924)F, P(4715)L, D(614)G | ORF1(2), S(1) | 2 |
| MT496977 | Ahmedabad | F(924)F, P(4715)L, D(614)G | ORF1(2), S(1) | 2 |
| MT481907 | Gandhinagar | F(924)F, P(4715)L, D(614)G | ORF1(2), S(1) | 2 |
| MT496996 | Gandhinagar | F(924)F, P(4715)L, D(614)G, I(692)I | ORF1(2), S(2) | 2 |
| MT481904 | Gandhinagar | F(924)F, P(4715)L, K(4803)K, D(614)G | ORF1(3), S(1) | 2 |
| MT481903 | Dahegam | F(924)F, P(4715)L, K(4803)K, D(614)G, L(116)L | ORF1(3), S(1), ORF7a(1) | 2 |
| MT481902 | Dahegam | F(924)F, P(4715)L, K(4803)K, D(614)G | ORF1(3), S(1) | 2 |
| MT481900 | Gandhinagar | F(924)F, P(4715)L, V(5999)V, D(614)G, I(692)I | ORF1(3), S(2) | 2 |
| MT496981 | Ahmedabad | P(4715)L, V(5272)I, L(6205)L, N(6629)N | ORF1(4) | 2 |
| MT451886 | Ahmedabad | P(4715)L, D(614)G, Q(677) H, | ORF1(1), S(2) | 3 |
| MT467260 | Prantij | F(924)F, T(3058)I, P(4715)L, D(614)G | ORF1(3), S(1) | 3 |
| MT467250 | Ahmedabad | F(924)F, P(4715)L, D(614)G, A(892)V | ORF1(2), S(2) | 3 |
| MT467249 | Ahmedabad | F(924)F, F(1960)F, P(4715)L, D(614)G, Q(677)H | ORF1(3), S(2) | 3 |
| MT467242 | Ahmedabad | F(924)F, P(4715)L, V(6600)A, D(614)G, I(692)I | ORF1(3), S(2) | 3 |
| MT467246 | Ahmedabad | F(924)F, P(4715)L, L(6205)L, D(614)G, Q(57)H, Y(71)Y | ORF1(3), S(1), ORF3a(1), M(1) | 3 |
| MT467238 | Ahmedabad | N(189)N, F(924)F, N(4550)N, M(4588)I, P(4715)L, D(614)G | ORF1(5), S(1) | 3 |
| MT435083 | Ahmedabad | G(662)R, F(924)F, L(2253)L, P(4715)L, V(6536)V, V(6660)V, D(614)G, I(692)I, | ORF1(6), S(2) | 3 |
| MT483559 | Prantij | F(924)F, T(3058)I, P(4715)L, D(614)G | ORF1(3), S(1) | 3 |
| MT483553 | Modasa | F(924)F, T(3058)I, P(4715)L, D(614)G | ORF1(3), S(1) | 3 |
| MT483555 | Modasa | F(924)F, N(3405)H/I, L(6205)L, D(614)G, Q(57)H, Y(71)Y | ORF1(4), S(1), ORF3a(1), M(1) | 3 |
| MT496973 | Ahmedabad | G(192)D, F(924)F, P(4715)L, D(614)G | ORF1(3), S(1) | 3 |
| MT481908 | Mansa | F(924)F, P(4715)L, L(6205)L, D(614)G, Q(57)H, Y(71)Y | ORF1 (3), S (1), ORF3a (1), M (1) | 3 |
Table 3.
Missense and silent mutations in the entire genome of SARS-CoV2 from Indian patients.
| Virus Genome ID | Location | Missense and silent mutations | Genomic regions | Missense mutation |
|---|---|---|---|---|
| MT509494 | Vadodara | S(443)S, F(924)F, D(1273)D, P(4715)L, G(5862)G, L(6082)F, D(614)G | ORF1 (6), S (1) | 3 |
| MT496997 | Gandhinagar | F(924)F, G(5530)C, L(6205)L, V(6385)L, V(6536)V, D(614)G, Q(57)H, Y(71)Y, D(225)D | ORF1 (5), S (1), ORF3a (2), M (1), M (1) | 3 |
| MT467240 | Ahmedabad | P(4715)L, L(4721)I, E(156)D, D(614)G | ORF1 (2), S (2) | 4 |
| MT477885 | India | T(2016)K, L(3606)F, A(4489)V, Y(789)Y, P(13)L | ORF1 (3), S (1), N (1) | 4 |
| MT435080 | Ahmedabad | F(924)F, A(4577)V, I(4593)L, P(4715)L, D(614)G | ORF1 (4), S (1) | 4 |
| MT467239 | Ahmedabad | L(3338)F, P(4715)L, L(6205)L, D(614)G, Q(57)H, Y(71)Y | ORF1 (3), S (1), ORF3a (1), M (1) | 4 |
| MT358637 | Rajkot | F(924)F, K(2067)K, P(4715)L, Q(271)R, D(614)G, R(41)R, T(393)I | ORF1 (3), S (2), N (2) | 4 |
| MT415323 | India | F(924)F, P(4715)L, D(614)G, R(203)K, G(204)R | ORF1 (2), S (1), N (2) | 4 |
| MT012098 | Kerala | I(671)T, P(2144)S, A(4798)V, A(5703)A, R(408)I | ORF1 (4), S (1) | 4 |
| MT451880 | Surat | T(2016)K, L(3606)F, A(3645)A, A(4489)V, F(5251)F, Y(789)Y, V(1264)V, P(13)L | ORF1 (5), S (2), N (1) | 4 |
| MT467259 | Prantij | F(924)F, P(4715)L, L(6205)L, D(614)G, Q(57)H, Y(71)Y, P(13)L | ORF1 (3), S (1), ORF3a (1), M (1), N (1) | 4 |
| MT467241 | Ahmedabad | F(924)F, S(1534)I, P(4715)L, L(4721)I, F(6251)F, D(614)G | ORF1 (5), S (1) | 4 |
| MT467237 | Ahmedabad | F(924)F, L(3338)F, P(4715)L, L(6205)L, D(614)G, Q(57)H, Y(71)Y | ORF1 (4), S (1), ORF3a (1), M (1) | 4 |
| MT457402 | Hyderabad | F(924)F, P(4715)L, L(6205)L, M to AYG, D(614)G, Q(57)H | ORF1 (4), S (1), ORF3a (1) | 4 |
| MT451885 | Ahmedabad | F(924)F, N(3405)H/I, P(4715)L, L(6205)L, D(614)G, Q(57)H, Y(71)Y | ORF1 (5), S (1), ORF3a (1), M (1) | 4 |
| MT467262 | Modasa | D(4117)D, P(4715)L, L(6205)L, R(78)M, D(614)G, Q(57)H, Y(71)Y | ORF1 (3), S (2), ORF3a (1), M (1) | 4 |
| MT467261 | Modasa | D(4117)D, P(4715)L, L(6205)L, R(78)M, D(614)G, Q(57)H, Y(71)Y | ORF1 (3), S (2), ORF3a (1), M (1) | 4 |
| MT467251 | Ahmedabad | F(924)F, Q(1084)Q, P(4715)L, L(6205)L, D(614)G, T(827)I, Q(57)H, Y(71)Y, D(225)D | ORF1 (4), S (2), ORF3a (1), M (1), N (1) | 4 |
| MT467248 | Ahmedabad | C(857)C, F(924)F, P(4715)L, L(6205)L, D(294)D, D(614)G, Q(57)H, Y(71)Y, S(194)L | ORF1 (4), S (2), ORF3a (1), M (1), N (1) | 4 |
| MT467245 | Ahmedabad | C(857)C, F(924)F, P(4715)L, L(6205)L, D(294)D, D(614)G, Q(57)H, Y(71)Y, S(194)L | ORF1 (4), S (2), ORF3a (1), M (1), N (1) | 4 |
| MT467255 | Ahmedabad | F(924)F, P(4715)L, L(5580)L, K(5957)R, L(6205)L, D(614)G, Q(57)H, Y(71)Y, G(70)G, Q(39)Q, D(225)D | ORF1 (5), S (1), ORF3a (1), M (1), ORF7a (1), N (2) | 4 |
| MT451887 | Ahmedabad | V(682)F, F(924)F, P(4715)L, D(5437)D, T(5775)T, D(614)G, G(236)C | ORF1(15), S (1), N (1) | 4 |
| MT483558 | Modasa | F(924)F, D(4117)D, P(4715)L, L(6205)L, R(78)M, D(614)G, Q(57)H, Y(71)Y | ORF1 (4), S (2), ORF3a (1), M (1) | 4 |
| MT483554 | Modasa | F(924)F, D(4117)D, P(4715)L, L(6205)L, R(78)M, D(614)G, Q(57)H, Y(71)Y | ORF1 (4), S (2), ORF3a (1), M (1) | 4 |
| MT483557 | Modasa | F(924)F, V(1345)V, N(3405)H/I, P(4715)L, L(6205)L, D(614)G, Q(57)H, Y(71)Y | ORF1 (6), S (1), ORF3a (1), M (1) | 4 |
| MT496989 | Ahmedabad | P(309)L, F(924)F, P(4715)L, F(2)L, D(614)G | ORF1 (3), S (2) | 4 |
| MT496975 | Ahmedabad | N(3405)H/I, P(4715)L, D(614)G, Q(57)H, Y(71)Y, | ORF1 (2),S (1), ORF3a (1), M (1) | 4 |
| MT481896 | Ahmedabad | F(924)F, P(4715)L, Y(5541)Y, M(177)I, D(294)D, D(614)G, Q(57)H, Y(71)Y | ORF1 (3), S (3), ORF3a (1), M (1) | 4 |
| MT496988 | Ahmedabad | F(924)F, A(3179)A, F(3614)F, P(4715)L, L(6205)L, D(614)G, V(1104)L, Q(57)H, Y(71)Y | ORF1 (5), S (2), ORF3a (1), M (1) | 4 |
| MT481899 | Modasa | F(924)F, D(4117)D, P(4715)L, L(6205)L, R(78)M, D(614)G, Q(57)H, Y(71)Y | ORF1 (4), S (1), ORF3a (1), M (1) | 4 |
| MT481897 | Modasa | F(924)F, D(4117)D, D(4275)D, P(4715)L, L(6205)L, R(78)M, D(614)G, Q(57)H, Y(71)Y | ORF1 (5), S (2), ORF3a (1), M (1) | 4 |
| MT509501 | Jamnagar | F(924)F, N(1123)N, I(2385)I, N(4235)N, P(4715)L, N(5020)N, L(5)F, S(162)I, D(614)G | ORF1 (6), S (3) | 4 |
| MT509508 | Jamnagar | C(857)C, F(924)F, L(1591)L, P(4715)L, L(6205)L, D(294)D, D(614)G, Q(57)H, Y(71)Y, S(194)L | ORF1 (5), S (2), ORF3a (1), M (1), N (1) | 4 |
| MT496979 | Ahmedabad | F(924)F, P(4715)L, G(5530)C, L(6205)L, D(614)G, Q(57)H, Y(71)Y | ORF1 (4), S (1), ORF3a (1), M (1) | 4 |
| MT509495 | Kodinar | F(924)F, P(3395)S, P(4715)L, L(6205)L, D(614)G, Q(57)H, Y(71)Y | ORF1 (4), S (1), ORF3a (1), M (1) | 4 |
| MT509506 | Rajkot | S(2839)S, D(3681)N, T(302)T, L(41)F, L(84)S, S(202)N | ORF1 (2), S (1), ORF3a (1), ORF8 (1), N (1) | 4 |
| MT050493 | Kerala | I(476)V, P(2079)L, S(2839)S, T(5538)I, A(930)V, L(84)S | ORF1 (4), S (1), ORF8 (1) | 5 |
| MT451889 | Ahmedabad | D(1939)G, T(2016)K, S(2242)P, A(4489)V, T(22)T, Y(789)Y, P(13)L | ORF (4), S (2), N (1) | 5 |
| MT467252 | Ahmedabad | F(924)F, P(1158)S, S(1534)I, L(2161)L, P(4715)L, L(4721)I, L(110)L, D(614)G | ORF1 (6), S (2) | 5 |
| MT467247 | Ahmedabad | F(924)F, P(1158)S, S(1534)I, L(4149)L, P(4715)L, L(4721)I, L(110)L, D(614)G | ORF1 (6), S (2) | 5 |
| MT451874 | Surat | G(519)S, S(2015)R, T(2016)K, L(2146)L, L(3606)F, A(4489)V, L(6420)L, Y(789)Y | ORF1 (7), S (1) | 5 |
| MT415322 | India | T(2016)K, L(4606)F, A(4489)V, Y(789)Y, P(13)L | ORF1 (3), S (1), N (1) | 5 |
| MT435085 | Gandhinagar | C(857)C, F(924)F, P(4715)L, V(5272)I, L(6205)L, D(294)D, D(614)G, Q(57)H, Y(71)Y, S(194)L | ORF1 (5), S (2), ORF3a (1), M (1), N (1) | 5 |
Table 4.
Missense and silent mutations in the entire genome of SARS-CoV2 from Indian patients.
| Virus Genome ID | Location | Missense and silent mutations | Genomic regions | Missense mutation |
|---|---|---|---|---|
| MT467258 | ahmedabad | C(857)C, F(924)F, P(4715)L, L(6205)L, D(294)D, T(572)I, D(614)G, Q(57)H, Y(71)Y, S(194)L | ORF1 (4), S (3), ORF3a (1), M (1), N (1) | 5 |
| MT467256 | ahmedabad | C(857)C, F(924)F, P(4715)L, L(6205)L, D(294)D, T(572)I, D(614)G, Q(57)H, Y(71)Y, S(194)L | ORF1 (4), S (3), ORF3a (1), M (1), N (1) | 5 |
| MT435086 | Mansa | F(924)F, K(1230)K, S(1534)I, P(4715)L, L(4721)I, D(614)G | ORF1 (5), S (1) | 5 |
| MT483560 | Modasa | F(924)F, L(3606)F, D(4117)D, P(4715)L, L(6205)L, R(78)M, D(614)G, Q(57)H, Y(71)Y | ORF1 (5), S (2), ORF3a (1), M (1) | 5 |
| MT483556 | Modasa | F(924)F, L(3606)F, D(4117)D, P(4715)L, L(6205)L, R(78)M, D(614)G, Q(57)H, Y(71)Y | ORF1 (5), S (2), ORF3a (1), M (1) | 5 |
| MT509504 | Rajkot | F(924)F, S(1534)I, P(4715)L, L(4721)I, N(7083)D, D(614)G | ORF1 (5), S (1) | 5 |
| MT496976 | Ahmedabad | F(924)F, I(2806)I, V(4181)I, P(4715)L, S(13)I, D(614)G, R(192)L | ORF1 (4), S (2), N (1) | 5 |
| MT509509 | Ahmedabad | F(924)F, P(4715)L, L(6205)L, E(583)D, D(614)G, H(1083)Q, Q(57)H, Y(71)Y | ORF1 (3), S (3), ORF3a (1), M (1) | 5 |
| MT496972 | Ahmedabad | F(924)F, P(4715)L, A(5770)A, L(6205)L, P(7034)L, D(614)G, Q(57)H, V(77)F, Y(71)Y | ORF1 (6), S (1), ORF3a (2), M (1) | 5 |
| MT509503 | Junagadh | F(924)F, N(1123)N, K(2029)E, P(4715)L, N(5020)N, D(614)G, I(35)T, L(53)F | ORF1 (5), S (1), ORF3a (2) | 5 |
| MT496992 | Ahmedabad | C(857)T, F(924)F, P(4715)L, L(6205)L, D(294)D, D(614)G, Q(57)H, Y(71)Y, H(73)H, S(194)L | ORF1 (4), S (2), ORF3a (1), M (1), ORF7a (1), N (1) | 5 |
| MT509499 | Jamnagar | C(857)C, F(924)F, L(1599)L, L(3606)F, P(4715)L, L(6205)L, D(294)D, D(614)G, Q(57)H, Y(71)Y, S(194)L | ORF1 (6), S (2), ORF3a (1), M (1), N (1) | 5 |
| MT496984 | Ahmedabad | F(924)F, P(4715)L, L(6205)L, D(614)G, Q(57)H, Y(71)Y, H(125)Y, P(302)S | ORF1 (3), S (1), ORF3a (1), M (2), N (1) | 5 |
| MT509512 | Dahod | V(1393)V, S(2015)R, T(2016)K, L(3606)F, T(4164)T, A(4489)V, L(6420)L, Y(789)Y, P(13)L | ORF1 (7), S (1), N (1) | 5 |
| MT509500 | Dahod | V(1393)V, S(2015)R, T(2016)K, L(3606)F, T(4164)T, A(4489)V, L(6420)L, Y(789)Y, P(13)L | ORF1 (7), S (1), N (1) | 5 |
| MT509511 | Rajkot | V(169)A, S(2839)S, D(3681)N, L(41)F, L(84)S, S(202)N | ORF1 (3), ORF3a (1), ORF8 (1), N (1) | 5 |
| MT457403 | Hyderabad | T(2016)K, L(3606)F, A(4489)V, Y(789)Y, P(13)L | ORF1 (3), S (1), N (1) | 6 |
| MT435081 | Ahmedabad | T(265)T, F(924)F, P(4715)L, T(5036)M, D(614)G, Q(57)H, E(110)STOP, S(32)I | ORF1 (4), S (1), ORF3a (1), ORF8 (1), N (1) | 6 |
| MT467263 | Dhansura | C(857)C, F(924)F, P(2046)L, P(4715)L, L(6205)L, L(54)F, D(294)D, D(614)G, Q(57)H, Y(71)Y, S(194)L | ORF1 (5), S (3), ORF3a (1), M (1), N (1) | 6 |
| MT467254 | Ahmedabad | V(751)V, C(857)C, F(924)F, K(4081)R, P(4715)L, L(6205)L, D(294)D, D(614)G, Q(57)H, | ||
| Y(71)Y, A(156)S, S(194)L | ORF1 (6), S (2), ORF3a (1), M (1), N (2) | 6 | ||
| MT467253 | Ahmedabad | C(857)C, F(924)F, Y(4424)Y, P(4715)L, L(6205)L, D(294)D, T(572)I, D(614)G, Q(57)H, Y(71)Y, I(121)L, S(194)L | ORF1 (5), S (3), ORF3a (1), M (1), ORF8 (1), N (1) | 6 |
| MT467243 | Ahmedabad | F(924)F, P(4715)L, D(5130)D, V(5272)I, L(6205)L, D(294)D, E(583)D, D(614)G, I(980)I, Q(57)H, Y(71)Y, S(194)L | ORF1 (5), S (4), ORF3a (1), M (1), N (1) | 6 |
| MT435082 | Ahmedabad | P(4715)L, P(5828)L, D(614)G, Q(57)H, E(110)STOP, S(33)I | ORF (2), S (1), ORF3a (1), ORF8 (1), N (1) | 6 |
| MT451877 | Surat | S(2839)I, F(3132)S, V(4746)L, T(302)T, G(38)V, L(84)S, S(202)N | ORF1 (3), S (1), ORF7a (1), ORF8 (1), N (1) | 6 |
| MT496995 | Gandhinagar | C(857)T, F(924)F, P(4715)L, V(5272)I, L(6205)L, D(294)D, D(614)G, Q(57)H, Y(71)Y, S(194)L | ORF1 (5), S (2), ORF3a (1), M (1), N (1) | 6 |
| MT496994 | Gandhinagar | C(857)T, F(924)F, P(4715)L, V(5272)I, L(6205)L, D(294)D, D(614)G, Q(57)H, Y(71)Y, S(194)L | ORF1 (5), S (2), ORF3a (1), M (1), N (1) | 6 |
| MT496982 | Ahmedabad | C(857)T, F(924)F, P(4715)L, L(6205)L, D(294)D, T(572)H, D(614)G, Q(57)H, Y(71)Y, S(194)L | ORF1 (4), S (3), ORF3a (1), M (1), N (1) | 6 |
| MT481906 | Gandhinagar | C(857)T, F(924)F, S(1733)G, P(4715)L, L(6205)L, D(294)D, D(614)G, Q(57)H, Y(71)Y, H(73)H, S(194)L | ORF1 (5), S (2), ORF3a (1), M (1), N (1) | 6 |
| MT481898 | Himatnagar | F(924)F, P(4715)L, V(5272)I, L(6205)L, D(294)D, E(583)D, D(614)G, Q(57)H, Y(71)Y, S(194)L | ORF1 (4), S (3), ORF3a (1), M (1), N (1) | 6 |
| MT496993 | Gandhinagar | C(857)T, F(924)F, P(4715)L, L(6205)L, D(294)D, D(614)G, A(706)S, Q(57)H, Y(71)Y, S(194)L | ORF1 (4), S (3), ORF3a (1), M (1), N (1) | 6 |
| MT496985 | Ahmedabad | F(924)F, P(4715)L, V(5272)I, L(6205)L, N(6629)N, D(294)D, E(583)D, D(614)G, Q(57)H, Y(71)Y, S(194)L | ORF1 (5), S (3), ORF3a (1), M (1), N (1) | 6 |
| MT496980 | Ahmedabad | C(857)C, F(924)F, P(4715)L, L(6205)L, L(54)F, D(294)D, D(614)G, Q(57)H, Y(71)Y, E(64)STOP, S(194)L | ORF1 (4), S (3), ORF3a (1), M (1), ORF8 (1), N (1) | 6 |
| MT481905 | Gandhinagar | F(924)F, P(4715)L, G(5530)C, L(6205)L, V(6385)L, V(6536)V, D(614)G, Q(57)H, L(86)W, Y(71)Y, D(225)D | ORF1 (6), S (1), ORF3a (2), M (1), N (1) | 6 |
| MT481901 | Dahegam | C(857)C, F(924)F, P(4715)L, V(4746)A, V(5272)I, L(6205)L, D(294)D, D(614)G, Q(57)H, Y(71)Y, S(194)L | ORF1 (6), S (2), ORF3a (1), M (1), N (1) | 6 |
Table 5.
Missense and silent mutations in the entire genome of SARS-CoV2 from Indian patients.
| Virus Genome ID | Location | Missense and silent mutations | Genomic regions | Missense mutation |
|---|---|---|---|---|
| MT509502 | Jamnagar | C(857)C, F(924)F, P(4715)L, G(6039)V, L(6205)L, L(54)F, D(294)D, D(614)G, Q(57)H, Y(71)Y, S(194)L | ORF1 (5), S (3), ORF3a (1), M (1), N (1) | 6 |
| MT496987 | Ahmedabad | C(857)C, F(924)F, P(4715)L, S(6059)S, L(6205)L, L(54)F, D(294)D, E(471)L, D(614)G, Q(57)H, Y(71)Y, S(194)L | ORF1 (5), S (4), ORF3a (1), M (1), N (1) | 6 |
| MT481895 | Ahmedabad | C(857)C, F(924)F, P(4715)L, Y(5541)Y, L(6205)L, M(177)I, D(294)D, D(614)G, Q(57)H, W(131)C, Y(71)Y, S(194)L | ORF1 (5), S (3), ORF3a (2), M (1), N (1) | 6 |
| MT509498 | Jamnagar | C(857)C, F(924)F, L(1599)L, P(4715)L, L(6205)L, L(6909)F, D(294)D, D(614)G, Q(57)H, Y(71)Y, S(194)L, D(348)Y | ORF1 (6), S (2), ORF3a (1), M (1), N (2) | 6 |
| MT509496 | Botad | S(2015)R, T(2016)K, L(2146)F, P(6805)S, Y(789)Y, S(31)L, P(13)L, | ORF1 (4), S (1), ORF7b (1), N (1) | 6 |
| MT451882 | Ahmedabad | C(857)C, F(924)F, E(4670)D, P(4715)L, L(6205)L, D(294)D, D(614)G, C(1243)F, Q(57)H, D(155)Y, Y(71)Y, S(194)L | ORF1 (5), S (3), ORF3a (2), M (1), N (1) | 7 |
| MT451888 | Ahmedabad | N(418)N, C(857)C, F(924)F, L(1852)L, T(1854)A, K(1973)R, P(4715)L, L(6205)L, L(54)F, D(294)D, D(614)G, Q(57)H, Y(71)Y, S(194)L | ORF1 (8), S (3), ORF3a (1), M (1), N (1) | 7 |
| MT496986 | Ahmedabad | C(857)T, F(924)F, P(2046)L, P(4715)L, L(6205)L, D(294)D, D(614)G, Q(57)H, Y(71)Y, G(120)R, S(194)L | ORF1 (5), S (2), ORF3a (1), M (1), N (2) | 7 |
| MT496983 | Ahmedabad | F(924)F, E(3962)K, P(4715)L, V(5272)I, L(6205)L, N(6629)N, D(294)D, E(583)D, D(614)G, Q(57)H, Y(71)Y, S(194)L | ORF1 (6), S (3), ORF3a (1), M (1), N (1) | 7 |
| MT496974 | Ahmedabad | F(924)F, P(4715)L, V(5272)I, L(6205)L, D(294)D, E(583)D, D(614)G, Q(57)H, A(143)S, Y(71)Y, S(194)L | ORF1 (4), S (3), ORF3a (2), M (1), N (1) | 7 |
| MT509505 | Ahmedabad | F(924)F, D(4117)D, P(4715)L, V(5272)I, L(6205)L, R(78)M, D(294)D, D(614)G, H(1083)Q, Q(57)H, Y(71)Y, S(194)L | ORF1 (5), S (4), ORF3a (1), M (1), N (1) | 7 |
| MT451881 | Ahmedabad | , C(857)C, F(924)F, E(4670)D, P(4715)L, L(6205)L, D(294)D, D(614)G, A(706)S, C(1243)F, Q(57)H, D(155)Y, Y(71)Y, S(194)L | ORF1 (5), S (4), ORF3a (2), M (1), N (1) | 8 |
| MT451876 | Surat | F(924)F, L(3606)F, D(4776)Y, P(4715)L, M(5974)I, L(6205)L, P(7034)S, D(614)G, K(1181)R, Q(57)H, Y(71)Y | ORF1 (7), S (2), ORF3a (1), M (1) | 8 |
| MT483702 | Modasa | F(924)F, Q(3390)R, T(3453)A, A(4273)V, P(4715)L, L(6205)L, R(78)M, D(614)G, Q(57)H, Y(71)Y, L(116)F | ORF1 (6), S (9), ORF3a (1), M (1), ORF7a (1), N (9) | 8 |
| MT496991 | Gandhinagar | C(857)C, F(924)F, P(4715)L, M(5060)I, L(6205)L, M(6723)I, D(294)D, D(614)G, Q(57)H, Y(71)Y, P(45)L, V(62)L, S(194)L | ORF1 (6), S (2), ORF3a (1), M (1), ORF7a (1), ORF8 (1), N (1) | 8 |
| MT509497 | Una | N(126)N, G(519)S, S(2015)R, T(2016)K, P(2739)L, L(3606)F, A(4489)V, L(6420)L, Q(677)H, Y(789)Y, P(13)L, A(152)S, | ORF1 (8), S (2), N (2) | 9 |
| MT509507 | Una | L(16)L, L(204)F, F(924)F, A(1812)D, L(3606)F, K(4451)N, P(4715)L, P(5624)L, K(6274)N, D(614)G, R(203)K, G(204)R, | ORF1 (9), S (1), N (2) | 10 |
| MT451890 | Ahmedabad | F(924)F, D(1939)G, T(2016)K, S(2242)P, D(4532)G, A(4489)V, P(4715)L, V(5272)I, L(6205)L, T(22)T, D(294)D, E(583)D, Y(789)Y, Q(57)H, S(171)L, P(13)L | ORF1 (10), S (4), ORF3a (2), N (1) | 11 |
| MT509510 | Una | L(16)L, L(204)F, F(924)F, A(1812)D, L(3606)F, K(4451)N, P(4715)L, P(5624)L, K(6274)N, D(614)G, G(8)E, R(203)K, G(204)R | ORF1 (9), S (1), ORF8 (1), N (2) | 11 |
Mutations of an amino acid A 1 to an amino acid A 2 is denoted by A 1 (l)A 2 where l denotes location of amino acid in the sequence. The third column of the Table 2, Table 3, Table 4, Table 5 describe the locations of amino acids where the mutations were detected. Here, in the fourth column the gene names are mentioned with the total number of mutations in the parenthesis.
1.1. Findings from the Table 2, Table 3, Table 4, Table 5
There are several missense mutations in the different genes across the genomes of SARS-CoV2 from Indian patients. Some of the conclusive inferences as well as hypotheses are drawn, based on the missense mutations as presented in the Table 2, Table 3, Table 4, Table 5 as follows:
-
•
Maximum number of missense mutations were found to be 11 which occurred in two genomes MT451890 (Ahmedabad-Gujarat) and MT509510(Una-Himachal Pradesh). Note that the only common missense mutations among these 11 mutations is P(4715)L. Therefore, we propose that these two patients (one from Gujarat and another from Himachal Pradesh, located 1300 KM apart) were infected by two different strains of the virus.
-
•
From Una, MT509507 genome has ten different missense mutations that are significantly different from others, which is depicted in the Table 5. So the patient carrying the SARS-CoV2 genome MT509507 has a distinct origin of infection.
-
•
No mutation was observed in the ORF6, E, ORF10 genes of the SARS-CoV2 genomes of the 128 strains. It is worth mentioning that among 128 genomes, MT509496 is the only genome where protein ORF7b possesses a missense mutation S(31)L. During this study (May 2020), SARS-CoV2 genome sequence from 128 Indian patients was available, but as on 14th July, 2020, SARS-CoV2 genome sequence from 339 Indian patients were available. Now, It is also checked that no missense mutation is present over the genes ORF6 and ORF10 in 339 virus sequences. This directly recommends that designing a therapeutic approach against these genes may have a significant role in prevention of COVID-19 pandemic, especially in India. It is further to be noted that one mutation V(62)F (N-terminus domain) in the envelope (E) gene of MT635409 genome (Nadiad, Gujarat) has been detected.
-
•
The six genomes MT451882, MT451888, MT496986, MT496983, MT496974 and MT509505 from Ahmedabad possess seven missense mutations among which only three are commons viz. P(4715)L, Q(57)H and S(194)L in the proteins ORF1, ORF3a and N respectively.
-
•
There are six identical missense mutations across the genomes MT496995 and MT496994 from Gandhinagar, which imply their same source of infection of COVID-19. Similarly, two genome sequences MT481898(Himatnagar) and MT496985(Ahmedabad), had six identical missense mutations and they are P(4715)L, V(5272)I, E(583)D, D(614)G, Q(57)H and S(194)L in the proteins ORF1, ORF1, S, S, ORF3a and N, respectively. So, the immediate source of infection of these two patients is either neighbouring or family patients.
-
•
Each pair of genomes {MT 467252, MT 467247} and {MT 467258, MT 467256} from Ahmedabad have five identical missense mutations across various proteins.
-
•
The pairs of genomes {MT 483558, MT 483554} and {MT 467262, MT 467261} from Modasa hold four identical (pairwise) mutations in ORF1, S, ORF3a and M proteins.
-
•
Except MT509503(Junagadh), all SARS-CoV2 genomes from 128 Indian patients had mutations at Q(57)H and Y(71)Y of the protein ORF3a and M respectively, apart from other mutations.
-
•
There are 13 genomes viz. MT451878, MT451883, MT451886, MT467240, MT467239, MT012098, MT451880, MT467262, MT467261, MT050493, MT451889, MT451874 and MT435082 where the missense mutations are restricted to the structural (except E) and non-structural proteins.
2. Conclusions
Several missense mutations over these 128 SARS-CoV2 genomes from Indian patients from diverse geo-locations show the wide genetic variations in a few of the SARS-CoV2 genes. Within a very small time frame, the virus evolved rapidly in most of the genes. Quite a few patients had identical mutations in SARS-CoV2 genes, indicating infection received from neighbouring or family patients. It will be interesting to study how many of these variations in the virus were carried by the patients from outside India or evolved within India. Whether the missense mutations over these 128 genomes lead to different functions of the proteins, is certainly the next question which is to be investigated by further studies. The hypotheses proposed in this article would be much stronger if the results are consistent while the number of SARS-CoV2 genomes from Indian patients increases significantly. Although the clinical significance of the observed mutations is not readily available, our findings lay the groundwork to understand the impact of SARS-CoV2 mutations on disease severity, host immune response, vaccine development and serological response.
Author contributions
SH, PPC, SSJ conceived the problem. SH determined the mutations. SH, PPC, BR and SSJ analysed the data and result. SH wrote the initial draft which was checked and edited by all other authors to generate the final version.
Declaration of Competing Interest
The authors do not have any conflicts of interest to declare.
Acknowledgments
Acknowledgement
Authors thank Pingla Thana Mahavidyalaya, Maligram, Paschim Medinipur, Indian Statistical Institute, Kolkata and Indian Association for the Cultivation of Science, Kolkata for their supports.
References
- 1.Singhal T. A review of coronavirus disease-2019 (covid-19) Indian J. Pediatr. 2020:1–6. doi: 10.1007/s12098-020-03263-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Stefanelli P., Faggioni G., Presti A.L., Fiore S., Marchi A., Benedetti E., Fabiani C., Anselmo A., Ciammaruconi A., Fortunato A. Whole genome and phylogenetic analysis of two sars-cov-2 strains isolated in Italy in january and february 2020: additional clues on multiple introductions and further circulation in Europe. Eurosurveillance. 2020;25(13) doi: 10.2807/1560-7917.ES.2020.25.13.2000305. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Cui J., Li F., Shi Z.-L. Origin and evolution of pathogenic coronaviruses. Nat. Rev. Microbiol. 2019;17(3):181–192. doi: 10.1038/s41579-018-0118-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Pachetti M., Marini B., Benedetti F., Giudici F., Mauro E., Storici P., Masciovecchio C., Angeletti S., Ciccozzi M., Gallo R.C. Emerging sars-cov-2 mutation hot spots include a novel rna-dependent-rna polymerase variant. J. Transl. Med. 2020;18:1–9. doi: 10.1186/s12967-020-02344-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Yu F., Du L., Ojcius D.M., Pan C., Jiang S. Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China. Microbes Infect. 2020;22(2):74–79. doi: 10.1016/j.micinf.2020.01.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Phan T. Genetic diversity and evolution of sars-cov-2. Infect. Genet. Evol. 2020;81 doi: 10.1016/j.meegid.2020.104260. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Hassan S.S., Choudhury P.P., Basu P., Jana S.S. Molecular conservation and differential mutation on orf3a gene in indian sars-cov2 genomes. Genomics. 2020;112(5):3226–3237. doi: 10.1016/j.ygeno.2020.06.016. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Hassan S.S., Choudhury P.P., Bidyut R. Sars-cov2 envelope protein: non-synonymous mutations and its consequences. Genomics. 2020;112(5):3890–3892. doi: 10.1016/j.ygeno.2020.07.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Badaoui B., Sadki K., Talbi C., Tazi L., Salah D. Genetic diversity and genomic epidemiology of sars-cov-2 in Morocco. bioRxiv. 2020 doi: 10.1016/j.bsheal.2021.01.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Panda G., Mishra N., Ray A. 2020. Genetic Variations and Drug Repurposing Provides Key Insights into the Disruption of the Sars Cov2. [Google Scholar]
- 11.Cai H.Y., Cai K.K., Li J. 2020. Identification of Novel Missense Mutations in a Large Number of Recent Sars-Cov-2 Genome Sequences. [Google Scholar]
- 12.Gupta R., Charron J., Stenger C., Painter J., Steward H., Cook T., Faber W., Frisch A., Lind E., Bauss J. Sars-cov2 (covid-19) structural/evolution dynamicome: insights into functional evolution and human genomics. bioRxiv. 2020 doi: 10.1074/jbc.RA120.014873. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.van Dorp L., Acman M., Richard D., Shaw L.P., Ford C.E., Ormond L., Owen C.J., Pang J., Tan C.C., Boshier F.A. Emergence of genomic diversity and recurrent mutations in sars-cov-2. Infect. Genet. Evol. 2020;83 doi: 10.1016/j.meegid.2020.104351. [DOI] [PMC free article] [PubMed] [Google Scholar]