Article Temporal Analysis of SARS-CoV-2 Variants during the COVID-19 Pandemic in Nepal Samrat Paudel , Amol Dahal and Hitesh Kumar Bhattarai *   Citation: Paudel, S.; Dahal, A.; Bhattarai, H.K. Temporal Analysis of SARS-CoV-2 Variants during the COVID-19 Pandemic in Nepal. COVID 2021, 1, 423–434. https:// doi.org/10.3390/covid1020036 Academic Editors: Maria Yavropoulou, Dimitrios Paraskevis and Sotirios Tsiodras Received: 16 September 2021 Accepted: 22 September 2021 Published: 26 September 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Department of Biotechnology, Kathmandu University, Dhulikhel P.O. Box 6250, Nepal; samrat.paudel@ku.edu.np (S.P.); amol.dahal@ku.edu.np (A.D.) * Correspondence: hitesh321@gmail.com Abstract: Nepal has suffered two waves of SARS-CoV-2 infections, one in the year 2020 and another in the year 2021. Although the government of Nepal keeps a detailed record of daily coronavirus infections and deaths throughout the country, and publishes the result every day, genomic surveil- lance of mutants in the country has lagged behind. Sequencing of COVID-19 samples has been conducted sporadically during the pandemic. From the GISAID database, 127 high-quality sequences deposited by different health authorities in Nepal were collected and analyzed. From the analysis, it can be concluded that at least two variants of concern, alpha and delta, and one variant of interest, kappa, were detected in Nepal in 2021. As in other countries, the delta variant outcompeted the kappa and alpha variants and by July 2021 had established itself as the dominant variant. It can be hypothesized that the second wave in Nepal was primarily caused by the delta variant. Further, phylogenetic tree analysis suggests cases of local transmission and global transmission of coronavirus. This analysis reveals the global nature of the disease, where variants arising in one part of the world can quickly spread to other parts of the world and can also spread through individual communities. This paper highlights a need to structure public policy of Nepal to target the delta variant since it has become the predominant variant in Nepal. A further policy suggestion is to appropriately sample and sequence genomes of SARS-CoV-2 at regular intervals to understand the dynamics of variants in the population. Keywords: COVID-19; Nepal; variants; delta; temporal; analysis; phylogenetic tree 1. Introduction Since the first identification of the SARS-CoV-2 virus in Wuhan [1], China, SARS-CoV-2 has spread throughout the world and caused a pandemic. Cases of COVID-19 have been reported in Nepal since its first case of COVID-19, a student returning from Wuhan [2]. Nepal, along with India, has suffered two waves of coronavirus infections, one in 2020 and another in 2021. As of September 2021, the government of Nepal has reported over 700,000 cases and over 10,000 deaths attributed to COVID-19 [3]. Like any virus found in nature, SARS-CoV-2 has undergone various rounds of muta- tions since infecting humans in 2019. The mutation rate of SARS-CoV-2 has been estimated to be about (1.19–1.31) × 10 -3 /site/year [4]. The SARS-CoV-2 genome encodes for at least 29 proteins. Sixteen are non-structural proteins, first translated as one protein, ORF1ab. Later, this protein is proteolytically cleaved into the 16 non-structural proteins. From other open reading frames, four structural proteins—S, N, E, and M—are transcribed and translated. There are other accessory proteins—NS3a, NS3b, NS6, NS7a, NS7b, NS8, NS9a, NS9b, and NS10—encoded by the genome of the virus [5]. Although mutations can happen in the genomic region encoding for any of these proteins, mutations in the S (Spike) protein, which encodes for a viral receptor that binds to angiotensin-converting enzyme (ACE2) are particularly important. Mutations in the S protein are known to contribute to higher transmissibility and infectivity of the virus [6,7]. COVID 2021, 1, 423–434. https://doi.org/10.3390/covid1020036 https://www.mdpi.com/journal/covid